Third generation oral contraceptive use and cardiovascular risk factors

  • Angela Döring
    GSF—Research, National Research Centre for Environment and Health, Institute of Epidemiology, Ingolstädter Landstr. 1, Neuherberg 85764, Germany
    Search for articles by this author
  • Margit Fröhlich
    Department of Internal Medicine VI, Clinical Pharmacology and Pharmacoepidemiology, University Hospital of Heidelberg, Heidelberg, Germany
    Search for articles by this author
  • Hannelore Löwel
    GSF—Research, National Research Centre for Environment and Health, Institute of Epidemiology, Ingolstädter Landstr. 1, Neuherberg 85764, Germany
    Search for articles by this author
  • Wolfgang Koenig
    Corresponding author. Present address: Medizinische Universitätsklinik, Abteilung Innere Medizin II, Robert-Kochstr. 8, 89081 Ulm, Germany. Tel.: +49-731-50024465; fax: +49-731-50033872.
    Department of Internal Medicine II, University of Ulm Medical Centre, Ulm, Germany
    Search for articles by this author


      Objective: To analyze the relationship between third generation oral contraceptive (OC) use and various cardiovascular risk factors—including markers of inflammation—in a population-based sample. Study population and methods: Data on OC use were obtained from women, aged 25–44 years participating in the MONICA Augsburg survey 1994–1995. Complete data were available from 841 women. Third generation OCs were defined as OCs containing desogestrel or gestodene, the remaining OC products were summarized in the group “other OC.” Results: Women taking third generation OCs had significantly higher C-reactive protein, fibrinogen, plasma viscosity, and HDL-cholesterol concentrations compared to the “other OC” group and non-users. In contrast, LDL-cholesterol was identical in the three groups. The analyses of interaction between smoking and OC use revealed that smoking women taking third generation pills had a less favourable pattern concerning inflammatory markers compared to women not on OC or using other products. Conclusion: Potentially harmful effects of OCs may arise from their positive association with the acute phase response. There is a close relationship with inflammatory markers in particular in women taking third generation OCs, which may, at least in part, contribute to the increased atherothrombotic risk, reported specifically in these women.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Jordan WM. Pulmonary embolism. Lancet 1961;ii:1146–7.

        • Kemmeren J.M.
        • Algra A.
        • Grobbee D.E.
        Third generation oral contraceptives and risk of venous thrombosis: meta-analyses.
        Br. Med. J. 2001; 323: 1-9
      2. WHO Collaborative study of cardiovascular disease and steroid hormone contraception. Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study. Lancet 1997;349:1202–9.

        • Tanis B.C.
        • van den Bosch M.A.A.J.
        • Kemmeren J.M.
        • Cats V.M.
        • Helmerhorst F.M.
        • Algra A.
        • et al.
        Oral contraceptives and the risk of myocardial infarction.
        N. Engl. J. Med. 2001; 345: 1787-1793
        • Dunn N.
        • Thorogood M.
        • Faragher B.
        • de Caestecker L.
        • MacDonald T.M.
        • McCullum C.
        • et al.
        Oral contraceptives and myocardial infarction: results of the MICA case-control study.
        Br. Med. J. 1999; 318: 1579-1584
        • Danesh J.
        • Collins R.
        • Appleby P.
        • Peto R.
        Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease. Meta-analyses of prospective studies.
        J. Am. Med. Assoc. 1998; 279: 1477-1482
        • Ridker P.M.
        • Hennekens C.H.
        • Rifai N.
        • Buring J.E.
        • Manson J.E.
        Hormone replacement therapy and increased plasma concentration of C-reactive protein.
        Circulation. 1999; 100: 713-716
        • Decensi A.
        • Omodei U.
        • Robertson C.
        • Bonanni B.
        • Guerrieri-Gonzaga A.
        • et al.
        Effect of transdermal estradiol and oral conjugated estrogen on C-reractive protein in retinoid-placebo trial in healthy women.
        Circulation. 2002; 106: 1224-1228
        • Silvestri A.
        • Gebara O.
        • Vitale C.
        • Waijngarten M.
        • Leonardo F.
        • et al.
        Increased levels of C-reactive protein after oral hormone replacement therapy may not be related to an increased inflammatory response.
        Circulation. 2003; 107: 3165-3169
      3. World Health Organisation Principal Investigators (prepared by H. Tunstall-Pedoe). The World Health Organization MONICA Project: a major international collaboration. J Clin Epidemiol 1988;34:105–14.

        • Hense H.W.
        • Filipiak B.
        • Döring A.
        • Stieber J.
        • Liese A.
        • Keil U.
        Ten-year trends of cardiovascular risk factors in the MONICA Augsburg Region in southern Germany. Results from the 1984–1985, 1989–1990, and 1994–1995 Surveys.
        CVD Prev. 1998; 1: 318-327
      4. Rote Liste. Verzeichnis von Fertigarzneimitteln der Mitglieder des Bundesverbandes der Pharmazeutischen Industrie e.V. Frankfurt 1994.

        • Woodward M.
        • Lowe G.
        • Rumley A.
        • Imhof A.
        • Koenig W.
        Measurement of plasma viscosity in stored frozen samples: a general population study.
        Blood Coagul. Fibrinolysis. 2003; 14: 417-420
        • Hutchinson W.L.
        • Koenig W.
        • Fröhlich M.
        • Sund M.
        • Lowe G.D.O.
        • Pepys M.B.
        Immunoradiometric assay of circulating C-reactive protein: age-related values in the adult general population.
        Clin. Chem. 2000; 46: 934-938
        • Crook D.
        • Godsland I.F.
        Safety evaluation of modern oral contraceptives.
        Contraception. 1998; 57: 189-201
        • Chasan-Taber L.
        • Stampfer M.J.
        Prospective study of oral contraceptives and hypertension among women in the United States.
        Circulation. 1996; 128: 483-489
        • Winkler U.H.
        Blood coagulation and oral contraceptives. A critical review.
        Contraception. 1998; 57: 203-239
        • Kluft C.
        • Lansink M.
        Effect of oral contraceptives on haemostasis variables.
        Thromb. Haemost. 1997; 78: 315-326
        • Gabay C.
        • Kushner I.
        Acute phase proteins and other systemic responses to inflammation.
        New Engl. J. Med. 1999; 340: 448-454
        • Fröhlich M.
        • Döring A.
        • Imhof A.
        • Hutchinson W.L.
        • Pepys M.B.
        • Koenig W.
        Oral contraceptive use is associated with a systemic acute phase response.
        Fibrinolysis Proteolysis. 1999; 13: 239-244
        • Danesh J.
        • Whincup P.
        • Walker M.
        • Lennon L.
        • Thomson A.
        • Appleby P.
        • et al.
        Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses.
        Br. Med. J. 2000; 321: 199-204
        • Lowe G.D.O.
        Rheological influences on thrombosis.
        Baillière’s Clin. Haematol. 1994; 7: 573-591
        • Chasan-Taber L.
        • Stampfer M.J.
        Epidemiology of oral contraceptives and cardiovascular disease.
        Ann. Intern. Med. 1998; 128: 467-477
        • Fotherby K.
        Metabolic interrelationships, cardiovascular disease, and sex steroids.
        Contraception. 1998; 57: 183-187
        • Godsland I.F.
        • Crook D.
        • Simpson R.
        • Proulder T.
        • Felton C.
        • Lees B.
        • et al.
        The effects of different formulations of oral contraceptive agents on lipid and carbohydrate metabolism.
        N. Engl. J. Med. 1990; 323: 1375-1381
        • Kuhl H.
        Effects of progestagens on haemostasis.
        Maturitas. 1996; 24: 1-19
        • Scarabin P.Y.
        • Vissac A.M.
        • Kirzin J.M.
        • Bourgeat P.
        • Amiral J.
        • Agher R.
        • et al.
        Elevated plasma fibrinogen and increased fibrin turnover among healthy women who both smoke and use low-dose oral contraceptives.
        Thromb. Haemost. 1999; 82: 1112-1116