Original research article| Volume 75, ISSUE 5, P344-354, May 2007

The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance study on Oral Contraceptives based on 142,475 women-years of observation



      The study was conducted to compare risks of adverse cardiovascular and other events associated with the use of drospirenone (DRSP)-containing oral contraceptives (OCs) and other OCs.

      Methods and Materials

      The European Active Surveillance study (EURAS) was a multinational, prospective, noninterventional cohort study of new users of DRSP, levonorgestrel (LNG) and other progestin-containing OCs. Semiannual follow-up was based on mailed questionnaires, with additional follow-up procedures when needed.


      Overall, 58,674 women were followed for 142,475 women-years of observation. Loss to follow-up was 2.4%. Serious adverse and fatal events were rare, and rate ratios were close to unity (1.0). Cox regression analysis of cardiovascular outcomes yielded hazard ratios for DRSP-containing vs. LNG-containing and other OCs of 1.0 and 0.8 (upper 95% confidence limits, 1.8 and 1.3) for venous, and 0.3 and 0.3 (upper 95% confidence limits, 1.2 and 1.5) for arterial thromboembolism, respectively.


      Risks of adverse cardiovascular and other serious events in users of a DRSP-containing OC are similar to those associated with the use of other OCs.


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        • World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception
        Effect of different progestagens in low oestrogen oral contraceptives on venous thromboembolic disease.
        Lancet. 1995; 346: 1582-1588
        • Jick H.
        • Jick S.S.
        • Gurewich V.
        • Myers M.W.
        • Vasilakis C.
        Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestagen components.
        Lancet. 1995; 346: 1589-1593
        • Spitzer W.O.
        • Lewis M.A.
        • Heinemann L.A.
        • Thorogood M.
        • MacRae K.D.
        Third generation oral contraceptives and risk of venous thromboembolic disorders: an international case-control study. Transnational Research Group on Oral Contraceptives and the Health of Young Women.
        BMJ. 1996; 312: 83-88
        • Bloemenkamp K.W.
        • Rosendaal F.R.
        • Helmerhorst F.M.
        • Buller H.R.
        • Vandenbroucke J.P.
        Enhancement by factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing a third-generation progestagen.
        Lancet. 1995; 346: 1593-1596
        • Kemmeren J.M.
        • Algra A.
        • Grobbee D.E.
        Third generation oral contraceptives and risk of venous thrombosis: meta-analysis.
        BMJ. 2001; 323: 131-134
        • Heinemann L.A.
        • Lewis M.A.
        • Assmann A.
        • Thiel C.
        Case control studies on venous thromboembolism: bias due to design? A methodological study on venous thromboembolism and steroid hormone use.
        Contraception. 2002; 65: 207-214
        • Preston R.A.
        • Alonso A.
        • Panzitta D.
        • Zhang P.
        • Karara A.H.
        Additive effect of drospirenone/17-beta-estradiol in hypertensive postmenopausal women receiving enalapril.
        Am J Hypertens. 2002; 15: 816-822
        • Krattenmacher R.
        Drospirenone: pharmacology and pharmacokinetics of a unique progestogen.
        Contraception. 2000; 62: 29-38
        • R��big A.
        Drospirenone: a new cardiovascular-active progestin with antialdosterone and antiandrogenic properties.
        Climacteric. 2003; 6: 49-54
        • Sch��rmann R.
        • Holler T.
        • Benda N.
        Estradiol and drospirenone for climacteric symptoms in postmenopausal women: a double-blind, randomized, placebo-controlled study of the safety and efficacy of three dose regime.
        Climacteric. 2004; 7: 189-196
        • Warming L.
        • Ravn P.
        • Nielsen T.
        • Christiansen C.
        Safety and efficacy of drospirenone used in a continuous combination with 17beta-estradiol for prevention of postmenopausal osteoporosis.
        Climacteric. 2004; 7: 103-111
        • Heinemann L.A.
        • Dinger J.
        Safety of a new oral contraceptive containing drospirenone.
        Drug Saf. 2004; 27: 1001-1018
        • Crosignani P.G.
        • La Vecchia C.
        Concordant and discordant effects on cardiovascular risks exerted by oestrogen and progestogen in women using oral contraception and hormone replacement therapy. ESHRE Capri Workshop Group.
        Hum Reprod Update. 1999; 5: 681-687
        • Suissa S.
        • Blais L.
        • Spitzer W.O.
        • Cusson J.
        • Lewis M.
        • Heinemann L.
        First-time use of newer oral contraceptives and the risk of venous thromboembolism.
        Contraception. 1997; 56: 141-146
        • Heinemann L.A.
        The changing scene: an unnecessary pill crisis.
        Hum Reprod Update. 1999; 5: 746-755
        • Lewis M.A.
        • MacRae K.D.
        • Kuhl-Habich D.
        • Bruppacher R.
        • Heinemann A.J.
        • Spitzer W.O.
        The differential risk of oral contraceptives: the impact of full exposure history.
        Hum Reprod. 1999; 14: 1493-1499
        • Lewis M.A.
        The Transnational Study on Oral Contraceptives and the Health of Young Women: methods, results, new analyses and the healthy user effect.
        Hum Reprod Update. 1999; 5: 707-720
        • Heinemann L.A.
        • Garbe E.
        • Farmer R.
        • Lewis M.A.
        Venous thromboembolism and oral contraceptive use: a methodological study of diagnostic suspicion and referral bias.
        Eur J Contracept Reprod Health Care. 2000; 5: 183-191
        • European Agency for the Evaluation of Medicinal Products
        Combined oral contraceptives and venous thromboembolism. The European Agency for the Evaluation of Medicinal Products Committee for Proprietary Medicinal Products (CPMP) public assessment report. London, 28 September 2001.
        ([online]. Available from URL) ([Accessed Oct. 30, 2006])
        • Heinemann L.A.
        • Dinger J.C.
        Range of published estimates of VTE incidence in young women.
        Contraception. 2007; 75: 328-336
        • Scurr J.H.
        • Machin S.J.
        • Bailey-King S.
        • Mackie I.J.
        • McDonald S.
        • Smith P.D.C.
        Frequency and prevention of symptomless deep-vein thrombosis in long-haul flights: a randomised trial.
        Lancet. 2001; 357: 1485-1489
        • Belcaro C.
        • Geroulakos G.
        • Nicolaides A.N.
        • Myers K.A.
        • Winford M.
        Venous thromboembolism from air travel: the LONFLIT Study.
        Angiology. 2001; 52: 369-374
        • Schwarz T.
        • Siegert G.
        • Oettler W.
        • et al.
        Venous thrombosis following long-haul flights.
        Arch Intern Med. 2003; 163: 2759-2764
        • Potthoff P.
        • Heinemann L.A.J.
        • G��ther B.
        A household panel as a tool for cost-effective health-related population surveys: validity of the ���Healthcare Access Panel���.
        Ger Med Sci. 2004; 2 (Doc05/20040716. Available from URL) ([Accessed Oct. 30, 2006])
        • G��ther B.
        Access panel ��� quality aspects and experience.
        in: Streich W. Braun B. Helmert U. Surveys in public health ��� developments and perspectives in research and political counseling. Asgard Verlag, Sankt Augustin2005: 91-102
        • Potthoff P.
        • G��ther B.
        Access panel in the context of health research.
        Forum Public Health. 2005; 13: 16
        • Grady W.R.
        • Hayward M.D.
        • Yagi J.
        Contraceptive failure in the United States: estimates from the 1982 National Survey of Family Growth.
        Fam Plann Perspect. 1986; 18: 200-209
        • Jones E.F.
        • Forrest J.D.
        Contraceptive failure rates based on the 1988 NSFG.
        Fam Plann Perspect. 1992; 24: 12-19
        • Fu H.
        • Darroch J.E.
        • Haas T.
        • Ranjit N.
        Contraceptive failure rates: new estimates from the 1995 National Survey of Family Growth.
        Fam Plann Perspect. 1999; 31: 56-563
        • Harrison-Woolrych M.
        • Ashton J.
        • Coulter D.
        Uterine perforation on intrauterine device insertion: is the incidence higher than previously reported?.
        Contraception. 2003; 67: 53-56
      1. Danish Health Registers.
        ([online]. Available from URL) ([Accessed Oct. 28, 2006])
        • Federal Statistical Office
        Statistical yearbook 2006 for the Federal Republic of Germany. Statistisches Bundesamt, Wiesbaden2006: 54