Skip to main content
SpringerLink
Log in

Hormontherapie bei Thrombophilie

Hormonal therapy in patients with thrombophilia

  • Leitthema
  • Published:
Der Gynäkologe Aims and scope

Zusammenfassung

Weibliche Sexualsteroide beeinflussen die Gerinnung und Fibrinolyse in vielfältiger Art und Weise. Dies erklärt, warum im Leben einer Frau das Thromboserisiko während der Schwangerschaft und im Wochenbett sowie unter der Einnahme von oralen kombinierten Kontrazeptiva bzw. während einer oralen östrogenhaltigen Hormontherapie steigt. Zudem erhöht sich das Thromboserisiko in Abhängigkeit des Lebensalters. Hereditäre und erworbene Thrombophilien sind selten, sie stellen jedoch einen relevanten zusätzlichen Risikofaktor für die Entwicklung einer venösen Thromboembolie unter Hormontherapie dar. Die Kenntnis über die gerinnungsphysiologischen Auswirkungen einer Hormontherapie, insbesondere in der Risikogruppe der Thrombophiliepatientinnen, reduziert das Risiko weiterer bzw. erstmaliger thromboembolischer Ereignisse. Im Rahmen des Beitrags sollen aktuelle Kenntnisse zum Einsatz einer Hormontherapie in diesem Risikokollektiv dargelegt werden.

Abstract

Female sexual steroids influence coagulation and fibrinolysis in different ways leading to an increased risk of thrombosis during pregnancy, confinement as well as during intake of oral contraceptives and hormonal therapy. Furthermore, a correlation between age and thrombotic risk is well known. Although hereditary and acquired thrombophilia are rare they have a major impact on the development of venous thromboembolism while undergoing hormonal therapy. Thrombotic events can be minimized by increasing the awareness of procoagulatory effects of hormonal therapy especially in women with thrombophilia. The aim of this review article is to summarize current knowledge concerning hormonal therapy in the subgroup of patients with thrombophilia.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2

Literatur

  1. Arden NK, Lloyd ME, Spector TD, Hughes GR (1994) Safety of hormone replacement therapy (HRT) in systemic lupus erythematosus (SLE). Lupus 3:11–13

    Article  PubMed  CAS  Google Scholar 

  2. Bagot CN, Marsh MS, Whitehead M et al (2010) The effect of estrone on thrombin generation may explain the different thrombotic risk between oral and transdermal hormone replacement therapy. J Thromb Haemost 8:1736–1744

    Article  PubMed  CAS  Google Scholar 

  3. Beral V, Banks E, Reeves G (2002) Evidence from randomised trials on the long-term effects of hormone replacement therapy. Lancet 360:942–944

    Article  PubMed  Google Scholar 

  4. Bertina RM (1999) Molecular risk factors for thrombosis. Thromb Haemost 82:601–609

    PubMed  CAS  Google Scholar 

  5. Buchanan GS, Rodgers GM, Ware Branch D (2003) The inherited thrombophilias: genetics, epidemiology, and laboratory evaluation. Best Pract Res Clin Obstet Gynaecol 17:397–411

    Article  PubMed  Google Scholar 

  6. Buyon JP, Petri MA, Kim MY et al (2005) The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial. Ann Intern Med 142:953–962

    PubMed  CAS  Google Scholar 

  7. Canonico M, Alhenc-gelas M, Plu-bureau G et al (2010) Activated protein C resistance among postmenopausal women using transdermal estrogens: importance of progestogen. Menopause 17:1122–1127

    Article  PubMed  Google Scholar 

  8. Chabbert-Buffet N, Amoura Z, Scarabin PY et al (2011) Pregnane progestin contraception in systemic lupus erythematosus: a longitudinal study of 187 patients. Contraception 83:229–237

    Article  PubMed  CAS  Google Scholar 

  9. Conard J, Plu-bureau G, Bahi N et al (2004) Progestogen-only contraception in women at high risk of venous thromboembolism. Contraception 70:437–441

    Article  PubMed  CAS  Google Scholar 

  10. Cosman F, Baz-hecht M, Cushman M et al (2005) Short-term effects of estrogen, tamoxifen and raloxifene on hemostasis: a randomized-controlled study and review of the literature. Thromb Res 116:1–13

    Article  PubMed  CAS  Google Scholar 

  11. Cushman M, Kuller LH, Prentice R (2004) Estrogen plus progestin and risk of venous thrombosis. JAMA 292:1573–1580

    Article  PubMed  CAS  Google Scholar 

  12. Dahlback B (1995) New molecular insights into the genetics of thrombophilia. Resistance to activated protein C caused by Arg506 to Gln mutation in factor V as a pathogenic risk factor for venous thrombosis. Thromb Haemost 74:139–148

    PubMed  CAS  Google Scholar 

  13. Daly E, Vessey MP, Hawkins MM et al (1996) Risk of venous thromboembolism in users of hormone replacement therapy. Lancet 348:977–980

    Article  PubMed  CAS  Google Scholar 

  14. Daly E, Vessey MP, Painter R, Hawkins MM (1996) Case-control study of venous thromboembolism risk in users of hormone replacement therapy. Lancet 348:1027

    Article  PubMed  CAS  Google Scholar 

  15. Douketis J (2005) Hormone replacement therapy and risk for venous thromboembolism: what’s new and how do these findings influence clinical practice? Curr Opin Hematol 12:395–400

    PubMed  CAS  Google Scholar 

  16. Douketis J, Julian J (2003) The effect of prothrombotic blood abnormalities on the association between hormone replacement therapy and venous thromboembolism. J Thromb Haemost 1:OC394

    Google Scholar 

  17. Eilertsen AL, Liestol S, Mowinckel MC et al (2007) Differential impact of conventional and low-dose oral hormone therapy (HT), tibolone and raloxifene on functionality of the activated protein C system. Thromb Haemost 97:938–943

    PubMed  CAS  Google Scholar 

  18. Gomes MP, Deitcher SR (2004) Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review. Arch Intern Med 164:1965–1976

    Article  PubMed  CAS  Google Scholar 

  19. Grady D, Wenger NK, Herrington D et al (2000) Postmenopausal hormone therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study. Ann Intern Med 132:689–696

    PubMed  CAS  Google Scholar 

  20. Greer IA (2003) Inherited thrombophilia and venous thromboembolism. Best Pract Res Clin Obstet Gynaecol 17:413–425

    Article  PubMed  Google Scholar 

  21. Grodstein F, Stampfer MJ, Goldhaber SZ et al (1996) Prospective study of exogenous hormones and risk of pulmonary embolism in women. Lancet 348:983–987

    Article  PubMed  CAS  Google Scholar 

  22. Herrington DM, Vittinghoff E, Howard TD et al (2002) Factor V Leiden, hormone replacement therapy, and risk of venous thromboembolic events in women with coronary disease. Arterioscler Thromb Vasc Biol 22:1012–1017

    Article  PubMed  CAS  Google Scholar 

  23. Hoibraaten E, Abdelnoor M, Sandset PM (1999) Hormone replacement therapy with estradiol and risk of venous thromboembolism–a population-based case-control study. Thromb Haemost 82:1218–1221

    PubMed  CAS  Google Scholar 

  24. Hulley S, Furberg C, Barrett-connor E et al (2002) Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 288:58–66

    Article  PubMed  CAS  Google Scholar 

  25. Jick H, Derby LE, Myers MW et al (1996) Risk of hospital admission for idiopathic venous thromboembolism among users of postmenopausal oestrogens. Lancet 348:981–983

    Article  PubMed  CAS  Google Scholar 

  26. Koster T, Blann AD, Briet E et al (1995) Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 345:152–155

    Article  PubMed  CAS  Google Scholar 

  27. Le Gal G, Gourlet V, Hogrel P et al (2003) Hormone replacement therapy use is associated with a lower occurrence of carotid atherosclerotic plaques but not with intima-media thickness progression among postmenopausal women. The vascular aging (EVA) study. Atherosclerosis 166:163–170

    Article  Google Scholar 

  28. Lidegaard O, Lokkegaard E, Svendsen AL, Agger C (2009) Hormonal contraception and risk of venous thromboembolism: national follow-up study. BMJ 339:b2890

    Article  PubMed  Google Scholar 

  29. Lowe G, Woodward M, Vessey M et al (2000) Thrombotic variables and risk of idiopathic venous thromboembolism in women aged 45–64 years. Relationships to hormone replacement therapy. Thromb Haemost 83:530–535

    PubMed  CAS  Google Scholar 

  30. Mansour D (2012) Safer prescribing of therapeutic norethisterone for women at risk of venous thromboembolism. J Fam Plann Reprod Health Care 38:148–149

    Article  PubMed  Google Scholar 

  31. Mantha S, Karp R, Raghavan V et al (2012) Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis. BMJ 345:e4944

    Article  PubMed  CAS  Google Scholar 

  32. Martinelli I, Mannucci PM, De Stefano V et al (1998) Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families. Blood 92:2353–2358

    PubMed  CAS  Google Scholar 

  33. Martinez F, Ramirez I, Perez-Campos E et al. (2012) Venous and pulmonary thromboembolism and combined hormonal contraceptives. Systematic review and meta-analysis. Eur J Contracept Reprod Health Care 17:7−29

    Article  PubMed  CAS  Google Scholar 

  34. Miller J, Chan BK, Nelson HD (2002) Postmenopausal estrogen replacement and risk for venous thromboembolism: a systematic review and meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med 136:680–690

    PubMed  CAS  Google Scholar 

  35. Mok CC, Lau CS, Ho CT et al (1998) Safety of hormonal replacement therapy in postmenopausal patients with systemic lupus erythematosus. Scand J Rheumatol 27:342–346

    Article  PubMed  CAS  Google Scholar 

  36. Mueck AO (2012) Postmenopausal hormone replacement therapy and cardiovascular disease: the value of transdermal estradiol and micronized progesterone. Climacteric 15(Suppl 1):11–17

    Article  PubMed  CAS  Google Scholar 

  37. Perez Gutthann S, Garcia Rodriguez LA, Castellsague J, Duque Oliart A (1997) Hormone replacement therapy and risk of venous thromboembolism: population based case-control study. BMJ 314:796–800

    Article  Google Scholar 

  38. Poort SR, Rosendaal FR, Reitsma PH, Bertina RM (1996) A common genetic variation in the 3’-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 88:3698–3703

    PubMed  CAS  Google Scholar 

  39. Psaty BM, Smith NL, Lemaitre RN et al (2001) Hormone replacement therapy, prothrombotic mutations, and the risk of incident nonfatal myocardial infarction in postmenopausal women. JAMA 285:906–913

    Article  PubMed  CAS  Google Scholar 

  40. Renoux C, Dell’aniello S, Suissa S (2010) Hormone replacement therapy and the risk of venous thromboembolism: a population-based study. J Thromb Haemost 8:979–986

    PubMed  CAS  Google Scholar 

  41. Ridker PM (2002) Inherited risk factors for venous thromboembolism: implications for clinical practice. Clin Cornerstone 4:18–30

    Article  PubMed  Google Scholar 

  42. Rosendaal FR, Vessey M, Rumley A et al (2002) Hormonal replacement therapy, prothrombotic mutations and the risk of venous thrombosis. Br J Haematol 116:851–854

    Article  PubMed  CAS  Google Scholar 

  43. Rossouw JE, Anderson GL, Prentice RL et al (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 288:321–333

    Article  PubMed  CAS  Google Scholar 

  44. Sanchez-Guerrero J, Villegas A, Mendoza-Fuentes A et al (2001) Disease activity during the premenopausal and postmenopausal periods in women with systemic lupus erythematosus. Am J Med 111:464–468

    Article  PubMed  CAS  Google Scholar 

  45. Scarabin PY, Oger E, Plu-Bureau G (2003) Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet 362:428–432

    Article  PubMed  CAS  Google Scholar 

  46. Toth B, Rogenhofer N, Budiman H et al (2006) Thrombophilia and female sex hormones. Curr Womens Health Rev 2:61–73

    Article  CAS  Google Scholar 

  47. Varas-Lorenzo C, Garcia-Rodriguez LA, Cattaruzzi C et al (1998) Hormone replacement therapy and the risk of hospitalization for venous thromboembolism: a population-based study in southern Europe. Am J Epidemiol 147:387–390

    Article  PubMed  CAS  Google Scholar 

Download references

Interessenkonflikt

Die korrespondierende Autorin gibt für sich und ihre Koautoren an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Gynäkologische Endokrinologie und Fertilitätsstörungen, Ruprecht-Karls-Universität Heidelberg, Voßstr. 9, 69115, Heidelberg, Deutschland

    B. Toth & C. Franz

  2. Medizinische Klinik, Klinikum Augsburg, Augsburg, Deutschland

    A. Rank

  3. amedes MVZ Zentrum für Endokrinologie, Kinderwunsch & Pränatale Medizin, Mönckebergstr. 10, 20095, Hamburg, Deutschland

    M. Ludwig

Authors
  1. B. Toth
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Rank
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Franz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Ludwig
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B. Toth.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Toth, B., Rank, A., Franz, C. et al. Hormontherapie bei Thrombophilie. Gynäkologe 46, 170–175 (2013). https://doi.org/10.1007/s00129-012-3072-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00129-012-3072-z

Schlüsselwörter

Keywords

Search

Navigation