Skip to main content
SpringerLink
Log in

Cardiology

  • Chapter
Estrogens and Antiestrogens II

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 135 / 2))

Abstract

Soon after the introduction of the first combined oral contraceptive (oq, Enovid lOR, in 1961, there appeared a case report that seemed to suggest a possible link between OC use and thromboembolic disease (JORDAN 1961). Thromboembolism is a part of the broader term “cardiovascular disease”. This chapter will exclusively discuss the relationship between OC use and thromboembolic diseases; the references cited are by necessity selective.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abbate R et al. (1990) Effects of long-term gestodene-containing oral contraceptive administration on hemostasis. Am J Obstet GynecoI163:424–429

    CAS  Google Scholar 

  • Bauer KA, Weitz 11 (1994) Laboratory markers of coagulation and fibrinolysis. In: Colman RW, Hirsh J, Marder VJ, Salzman EW (eds) Hemostasis and thrombosis. Basic principles and clinical practice. 3rd edn. Lippincott, Philadelphia, PA, p 1197

    Google Scholar 

  • Beller FK, Ebert C (1985) Effects of oral contraceptives on blood coagulation. A review. Obstet Gynecol Surv 40:425–436

    Article  CAS  Google Scholar 

  • Bellinger DA et al. (1998) Oral contraceptives and hormone replacement therapy do not increase the incidence of arterial thrombosis in a nonhuman primate model. Arterioscler Thromb Vasc BioI 18:92–99

    Article  CAS  Google Scholar 

  • Bertina RM et al. (1994) Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 369:64–67

    Article  PubMed  CAS  Google Scholar 

  • Bick RL, Murano G (1993) Physiology of hemostasis. In: Bick RL (ed) Hematology. Clinical and laboratory practice. Mosby, St. Louis, MO, p 84

    Google Scholar 

  • Bloemenkamp KWM (1995) Enhancement of factor V Leiden mutation of risk of deep-vein thrombosis associated with oral contraceptives containing third generation progestagen. Lancet 346:1589–1593

    Article  Google Scholar 

  • Blomback M et al. (1997) The effect of progesterone on the haemostatic mechanism. Thromb Haemostas 77:105–108

    CAS  Google Scholar 

  • Bokarewa MI et al. (1995) Thrombotic risk factors and oral contraceptives. J Lab Clin Med 126:294–298

    PubMed  CAS  Google Scholar 

  • Buring JE (1996) Low-dose oral contraceptives and stroke. N Engl J Med 335:53–55

    Article  PubMed  CAS  Google Scholar 

  • Broze GJ Jr, Tollefsen DM (1994) Regulation of blood coagulation by protease inhibitors. In: Stamatoyannopoulos G, Nienhuis AW, Majerus PW, Varmus H (eds) The molecular basis of blood diseases. 2nd edn. Saunders, Philadelphia, PA, p 629

    Google Scholar 

  • Coata G et al. (1995) Effect of low-dose oral triphasic contraceptives on blood viscosity, coagUlation and lipid metabolism. Contraception 52:151–157

    Article  PubMed  CAS  Google Scholar 

  • Colman RW et al. (1994) Overview of hemostasis. In: Colman RW, Hirsh J, Marder VJ, Salzman EW (eds) Hemostasis and thrombosis. Basic principles and clinical practice. 3rd edn. Lippincott, Philadelphia, PA, p 3

    Google Scholar 

  • Comp PC (1986) Hereditary disorders predisposing to thrombosis.Progr Hemostas Thromb 8:71–102

    CAS  Google Scholar 

  • Comp PC (1997) Thrombophilic mechanisms of OCs. Int J Fertil42 (Suppl1):170–176

    CAS  Google Scholar 

  • Creatsas G et al. (1997) Effects of two combined monophasic and triphasic ethinylestradiol/gestodene oral contraceptives on natural inhibitors and other hemostatic variables.Eur J Contracept Reprod Health Care 2:31–38

    Article  PubMed  CAS  Google Scholar 

  • Cumming AM et al. (1995) Development of resistance to activated protein C in pregnancy. Br J Haematol90:725–727

    Article  PubMed  CAS  Google Scholar 

  • Dahlback B et al. (1993) Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response of activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 90:1004–1008

    Article  PubMed  CAS  Google Scholar 

  • Douketis JD et al. (1997) A reevaluation of the risk for venous thromboembolism with the use of oral contraceptives and hormone replacement therapy.Arch Intern Med 157:1522-1530

    Article  Google Scholar 

  • Esmon CT (1984) Protein C. Semin Thromb Hemostas 10:109–166

    Article  Google Scholar 

  • Farag AM et al. (1988) Oral contraceptives and the hemostasis system. Obstet Gynecol 71:584–588

    PubMed  CAS  Google Scholar 

  • Fareed J (1984) Molecular markers of hemostatic disorders.Semin Thromb Hemostas 10:215–332

    Article  Google Scholar 

  • Farley TMM et al. (1995) Effect of different progestagens in low estrogen oral contraceptives on venous thromboembolism.Lancet 346:1582–1588

    Google Scholar 

  • Farmer RTD et al. (1997) Population-based study of risk of venous thromboembolism associated with various oral contraceptives.Lancet 349:83–88

    Article  PubMed  CAS  Google Scholar 

  • Fotherby K (1996) Thrombosis and the pill (guest editorial).J Drug Dev Clin Pract 8:1–5

    CAS  Google Scholar 

  • Gerstman et al. (1990) Oral contraceptive estrogen and progestin potencies and the incidence of deep venous thrombosis.Int J Epidemiol19:931–936

    Article  Google Scholar 

  • Gevers Leuven JA et al. (1996) Effects of low-dose ethinylestradiol oral contraceptives differing in progestogen compound on coagulation and fibrinolytic-risk variables for venous and arterial thromboembolic diseases. In: Glas-Greenwalt P (ed) Fibrinolysis diseases. CRC, Boca Raton, FL, p 226

    Google Scholar 

  • Girolami A et al. (1995) Patients with APC resistance compared with those with other clotting inhibitor deficiencies show late onset of venous thrombosis during oral contraception.Clin Appl Thromb/Hemostas 1:274–276

    Article  Google Scholar 

  • Gram J et al. (1990) Enhanced generation and resolution of fibrin in women above the age of 30 years using oral contraceptives low in estrogen.Am J Obstet Gynecol 163:438–442

    PubMed  CAS  Google Scholar 

  • Harker LA, Mann KG (1992) Thrombosis and fibrinolysis. In: Fuster V, Verstraete M (eds) Thrombosis in cardiovascular disorders. Saunders, Philadelphia, PA, p 1

    Google Scholar 

  • Hellgren M et al. (1995) Resistance to activated protein C as a basis for venous thromboembolism associated with pregnancy and oral contraceptives. Am J Obstet Gynecol 173:210–213

    Article  PubMed  CAS  Google Scholar 

  • Hultin MB (1991) Fibrinogen and factor VII as risk factors in vascular disease. Progr Hemostas Thromb 10:215–241

    CAS  Google Scholar 

  • Inman WHW, Vessey MP (1968) Investigation of deaths from pulmonary, coronary and cerebral thrombosis and embolism in women of childbearing age. Br Med J 2:193–199

    Article  PubMed  CAS  Google Scholar 

  • Inman WHW et al. (1970) Thromboembolic disease and the steroidal content of oral contraceptives: A report to the Committee on Safety of Drugs. Br Med J 2:203–209

    Article  PubMed  CAS  Google Scholar 

  • Jespersen J, Gram J (1996) Increased fibrin formation in blood of women above the age of 30 who are both oral contraceptive users and smokers. Fibrinolysis 10:9–13

    Article  CAS  Google Scholar 

  • Jick H et al. (1995) Risk of idiopathic cardiovascular death and nonfatal venous thromboembolism in women using oral contraceptives with differing progestogen components.Lancet 346:1589–1593

    Article  PubMed  CAS  Google Scholar 

  • Jick H et al. (1996) Risk of acute myocardial infarction and low-dose combined oral contraceptives (Letter).Br Med J 347:627–628

    CAS  Google Scholar 

  • Jordan WM (1961) Pulmonary embolism.Lancet 11:1146–1147

    Article  Google Scholar 

  • Koster T et al. (1993) Venous thrombosis due to poor anticoagulant responses to activated protein C: Leiden thrombophilia study. Lancet 342:1503–1506

    Article  CAS  Google Scholar 

  • Lewis MA et al. (1996a) The increased risk of venous thromboembolism and the use of third generation progestagens: Risk of bias in observational research.Contraception 54:5–13

    Article  PubMed  CAS  Google Scholar 

  • Lewis MA et al. (1996b) Third generation oral contraceptives and risk of myocardial infarction: An international case-control study.Br Med J 312:88–90

    Article  CAS  Google Scholar 

  • Lidegaard 0, Milson I (1996) Oral contraceptives and thrombotic diseases: Impact of new epidemiological studies. Contraception 53:135–139

    Article  PubMed  CAS  Google Scholar 

  • Lijnen HR, Collen D (1989) Congenital and acquired deficiencies of components of the fibrinolytic syndrome and their relation to bleeding and thrombosis. Fibrinolysis 3:62–77

    Article  Google Scholar 

  • Lox CD (1996) Biochemical effects in women following one year’s exposure to a new triphasic oral contraceptive.II. Coagulation profiles. Gen PharmacoI27:371–374

    CAS  Google Scholar 

  • Mammen EF (1982) Oral contraceptives and blood coagulation: A critical review. Am J Obstet GynecoI142:781–790

    CAS  Google Scholar 

  • Mammen EF (1992a) Oral contraceptives and thrombotic risk: A critical overview. In: Ramwell P, Rubanyi G, Schillinger E (eds) Sex steroids and the cardiovascular system. Springer, Berlin Heidelberg New York, p 65

    Google Scholar 

  • Mammen EF (1992b) Pathogenesis of venous thrombosis. Chest 102:640S–644S

    PubMed  CAS  Google Scholar 

  • Mammen EF (1994) Ten years experience with the “sticky platelet syndrome”.Clin Appl Thromb/Hemostas 1:66–72

    Article  Google Scholar 

  • Mammen EF, Fujii Y (1989) Hypercoagulable states. Lab Med 20:611–615

    Google Scholar 

  • Mammen EF, Wilson RF (1996) Coagulation abnormalities in trauma. In: Wilson RF, Walt AJ (eds). Management of trauma. Pitfalls and practice. 2nd edn. Williams and Wilkins, Baltimore, MD, p 1012

    Google Scholar 

  • Mann JI et al. (1975) Oral contraceptives and myocardial infarction in young women: A further report.Br Med J 3:631–632

    Article  PubMed  CAS  Google Scholar 

  • Manning JM et al. (1997) Effects of contraceptive estrogen and progestin on the atherogenic potential of plasma LDLs in cynomolgus monkeys.Arteriosc1er Thromb Vasc BioI 17:1216–1223

    Article  CAS  Google Scholar 

  • Meade TW (1988) Risks and mechanisms of cardiovascular events in users of oral contraceptives.Am J Obstet GynecoI158:1646–1652

    CAS  Google Scholar 

  • Melis GBet al. (1990) A comparative study on the effects of monophasic pill containing desogestrel plus 20 micrograms ethinylestradiol, a triphasic combination containing levonorgestrel and a monophasic combination containing gestodene on coagulation factors.Contraception 43:23–31

    Article  Google Scholar 

  • Norris LA, Bonnar J (1996) The effect of estrogen dose and progestogen type on haemostatic changes in women taking low dose oral contraceptives. Br J Obstet GynecoI103:261–267

    Article  CAS  Google Scholar 

  • Notolovitz M (1985) Oral contraception and coagulation.Clin Obstet Gynecol 28:73–83

    Article  Google Scholar 

  • Olivieri 0 et al. (1995) Resistance to activated protein C in healthy women taking oral contraceptives. Br J Haematol 91:465–470

    Article  PubMed  CAS  Google Scholar 

  • Olivieri 0 et al. (1996) Resistance to activated protein C, associated with oral contraceptives use; effect of formulations, duration of assumption, and doses of oestroprogestins. Contraception 54:149–152

    Article  PubMed  CAS  Google Scholar 

  • Partan Cet al. (1991) Effect of contraceptive pill containing 0.03mg ethinylestradiol and 0.075mg gestogen on blood coagulation and fibrinolysis.Thromb Haemostas 65:894 (Abst)

    Google Scholar 

  • Petersen KR et al. (1993) Effects of monophasic low-dose oral contraceptives on fibrin formation and resolution in young women.Am J Obstet GynecoI168:32–38

    CAS  Google Scholar 

  • Petitti DB et al. (1996) Stroke in users of low-dose oral contraceptives. N Engl J Med 335:8–15

    Article  PubMed  CAS  Google Scholar 

  • Poller Lfor the Task Force on Oral Contraceptives-WHO (1991) A multicentre study of coagUlation and haemostatic variables during oral contraception: Variations with four formulations. Br J Obstet GynecoI98:1117–1128

    Google Scholar 

  • Poulter NR et al. (1995) Venous thromboembolic disease and combined oral contraceptives: Results of international multicentre case-control study.Lancet 346:1575–1582

    Google Scholar 

  • Quehenberg Pet al. (1997) Effects of third generation oral contraceptives containing newly developed progestagens on fibrinolytic parameters.Fibrinolysis Proteolysis 11:97–101

    Article  Google Scholar 

  • Realini JP, Goldzieher IN (1985) Oral contraceptives and cardiovascular disease: A critique of the epidemiological studies. Am J Obstet Gynecol152:729–798

    Google Scholar 

  • Rees DC (1996) The population genetics of factor V Leiden (Arg 506 Gln).Br J Haematol95:579–586

    Article  Google Scholar 

  • Robinson GE (1994) Low-dose combined oral contraceptives.Br J Obstet Gynaecol 101:1036–1041

    Article  PubMed  CAS  Google Scholar 

  • Royal College of General Practitioners (1974) Oral contraceptives and health. Pitman, London

    Google Scholar 

  • Royal College of General Pr actitioners (1978) Oral contraceptives, venous thrombosis, and varicose veins. J Royal Coll Gen Pract 28:393-399

    Google Scholar 

  • Saleh AA et al. (1994) TAT complexes and prothrombin fragment 1+2 in oral contraceptive users.Thromb Res 73:137–142

    Article  PubMed  CAS  Google Scholar 

  • Saleh AA et al. (1995) Hormonal contraception and platelet function.Thromb Res 78:363–367

    Article  PubMed  CAS  Google Scholar 

  • Scarabin P-Yet al.(1995) Changes in haemostatic variables induced by oral contraceptives containing 50J.1g or 30J.1g estrogen: Absence of dose-dependent effect on PAI-1 activity.Thromb Haemostas 74:928–932

    CAS  Google Scholar 

  • Schambeck CM et al. (1997) Selective screening for the factor V Leiden mutation: Is it advisable prior to the prescription of oral contraceptives? Thromb Haemostas 78:1480–1483

    CAS  Google Scholar 

  • Schwingl PJ, Shelton J (1997) Modeled estimates of myocardial infarction and venous thromboembolic disease in users of second and third generation oral contraceptives. Contraception 55:125–129

    Article  PubMed  CAS  Google Scholar 

  • Spitzer WOet al. (1996) Third generation oral contraceptives and risk of venous thromboembolic disorders: An international case-control study.Br Med J 312:83–88

    Article  CAS  Google Scholar 

  • Svensson PJ, Dahlback B (1994) Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 330:517–522

    Article  PubMed  CAS  Google Scholar 

  • Thorogood M, Vessey MP (1990) An epidemiological survey of cardiovascular disease in women taking oral contraceptives. Am J Obstet Gynecol163:274–281

    Google Scholar 

  • Tikkanen MJ (1990) Role of plasma lipoproteins in the pathogenesis of atherosclerotic disease, with special reference to sex hormone effects.Am J Obstet Gynecol 163:296–304

    PubMed  CAS  Google Scholar 

  • Vandenbrouckeet al. (1994) Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation.Lancet 344:1453–1457

    Article  PubMed  CAS  Google Scholar 

  • Weinges KFet al. (1995) The effects of two phasic oral contraceptives on hemostasis and platelet function.Adv Contracept 11:227–237

    Article  PubMed  CAS  Google Scholar 

  • Winkler UHet al. (1991) Changes of the dynamic equilibrium of hemostasis associated with the use of low-dose oral contraceptives: A controlled study of cyproterone acetate containing oral contraceptives combined with either 35 or 50J.1g ethinyl estradiol.Adv Contraception 7 (Suppl 3):273–284

    Google Scholar 

  • Winkler UHet al. (1995) Hemostatic effects of two oral contraceptives containing low doses of ethinyl estradiol and either gestodene or norgestimate: An open, randomized, parallel-group study.Int J Fertil 40:260–268

    CAS  Google Scholar 

  • Winkler UH et al. (1996a) The influence of a low-dose oral contraceptive containing 20J.1g ethinylestradiol and 75J.1g gestodene on lipid and carbohydrate metabolism and hemostasis. In: Lopes P, Killick SR (eds) New option low-dose oral contraceptive. Parthenon, Carnfouth, p 49

    Google Scholar 

  • Winkler UH et al. (1996b) A comparative study of the effects on the hemostatic system of two monophasic gestodene oral contraceptives containing 20J.1g and 30J.1g ethinylestradiol. Contraception 53:75–84

    Article  PubMed  CAS  Google Scholar 

  • Winkler DH et al. (1996c) Ethinylestradiol20 versus 30,ugcombined with 150,ug desogestrel: A lare comparative study of the effects of two low-dose oral contraceptives on the hemostatic system.Gynecol Endocrinol 10:265–271

    Article  PubMed  CAS  Google Scholar 

  • Winkler DH et al. (1996d) Routine screening for coagulation inhibitors prior to prescribing the pill: Prevalence data from a large cohort of German pill starters.Eur J Contraception Reprod Health Care 1:47–52

    Article  CAS  Google Scholar 

  • Zoller B et al. (1997) Activated protein C resistance: Clinical implications.Clin Appl ThromblHemostas 3:25–32

    Google Scholar 

Download references

Authors
  1. E. F. Mammen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Mammen, E.F. (1999). Cardiology. In: Estrogens and Antiestrogens II. Handbook of Experimental Pharmacology, vol 135 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60107-1_22

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-60107-1_22

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-64261-6

  • Online ISBN: 978-3-642-60107-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation