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Review article: Biomedical intelligence

Vol. 146 No. 2122 (2016)

Genetic testing to identify women at risk of venous thromboembolism with contraceptive pills: evidence- or hope-based tool?

  • Marc Blondon
  • Françoise Boehlen
  • Pierre Fontana
  • Patrick Petignat
Cite this as:
Swiss Med Wkly. 2016;146:w14321


Combined oestrogen-progestin oral contraceptives cause venous thromboembolism in women of reproductive age. Healthcare providers typically rely on women’s characteristics, medical history and family history to select the most appropriate contraceptives, in an effort to reduce risks of venous thromboembolism. This position paper discusses the use of a new prediction tool (Pill Protect®), available in Switzerland, which adds genetic profiling to clinical characteristics with the aim of predicting individual contraceptive-related thrombotic risks and individualising contraceptive prescription. After reviewing the available data regarding this tool, we believe that its development and validation process may be incomplete and that it is uncertain whether the use of Pill Protect® would lead to better health outcomes. Until we understand the necessarily rigorous scientific validation of this tool, we urge caution to physicians and women who may want to use it.


  1. Dragoman MV. The combined oral contraceptive pill – recent developments, risks and benefits. Best Pract Res Clin Obstet Gynaecol. 2014;28:825–34. 10.1016/j.bpobgyn.2014.06.003.
  2. van Hylckama Vlieg A, Middeldorp S. Hormone therapies and venous thromboembolism: where are we now? J Thromb Haemost. 2011;9:257–66. 10.1111/j.1538-7836.2010.04148.x.
  3. Swissmedic. Contraceptifs hormonaux combinés (CHC) contenant de la chlormadinone ou de la drospirénone – suppression des mentions relatives aux avantages concernant l’acné (Indication/Propriétés) en raison du risque de thromboembolie veineuse (TEV) chez les utilisatrices de CHC. 2015. webpage; accessed on 12/01/2016.
  4. Merki-Feld GS, Bitzer J, Seydoux J, Birkhaüser M. Société Suisse de Gynécologie et Obstétrique: Handout destiné aux médecins pour la prescription de contraceptifs hormonaux combinés (CHC). webpage​informationen/​1_Expertenbriefe/Fr/Handout_destine_aux_medecins_​pour_la_prescription_de_contraceptifs_hormonaux_combines_2013.pdf; accessed on 30/11/2015.
  5. Faculty of Sexual & Reproductive Healthcare Statement. Venous thromboembolism (VTE) and Hormonal Contraception. 2014. webpage; accessed on 21/01/2016.
  6. Haute Autorité de Santé. Recommandations en Santé Publique: Dépistage systématique de la thrombophilie avant une primo-prescription de contraception hormonale combinée. 2015. webpage ; accessed on 21/01/2016.
  7. Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report: U.S. Medical Eligibility Criteria for Contraceptive Use, 2010. 4th Edition. webpage; accessed on 21/01/2016.
  8. Stegeman BH, de Bastos M, Rosendaal FR, van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, Dekkers OM. Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis. BMJ. 2013;347:f5298. 10.1136/bmj.f5298.
  9. Gene Predictis. Pill Protect® The first clinically validated test for identifying women at risk of developing deep vein thrombosis (DVT) under contraceptive pills. webpage; accessed on 30/11/2015.
  10. Suchon P, Al Frouh F, Henneuse A, Ibrahim M, Brunet D, Barthet MC, et al. Risk factors for venous thromboembolism in women under combined oral contraceptive. The PILl Genetic Risk Monitoring (PILGRIM) Study. Thromb Haemost. 2015;114. 10.1160/TH15-01-0045.
  11. Pepe MS. The Statistical Evaluation of Medical Tests for Classification and Prediction. Oxford Statistical Science Series. Oxford: Oxford University Press; 2003.
  12. Ioannidis JP, Ntzani EE, Trikalinos TA, Contopoulos-Ioannidis DG. Replication validity of genetic association studies. Nat Genet. 2001;29:306–9. 10.1038/ng749.
  13. Hendriksen JM, Geersing GJ, Moons KG, de Groot JA. Diagnostic and prognostic prediction models. J Thromb Haemost. 2013;11(Suppl 1):129–41. 10.1111/jth.12262.
  14. Salari K, Watkins H, Ashley EA. Personalized medicine: hope or hype? Eur Heart J. 2012;33:1564–70. 10.1093/eurheartj/ehs112.
  15. Reitsma PH, Rosendaal FR. Past and future of genetic research in thrombosis. J Thromb Haemost. 2007;5(Suppl 1):264–9. 10.1111/j.1538-7836.2007.02502.x.
  16. Ware JH. The limitations of risk factors as prognostic tools. N Engl J Med. 2006;355:2615–7. 10.1056/NEJMp068249.
  17. de Haan HG, Bezemer ID, Doggen CJ, Le Cessie S, Reitsma PH, Arellano AR, et al. Multiple SNP testing improves risk prediction of first venous thrombosis. Blood. 2012;120:656–63. 10.1182/blood-2011-12-397752.
  18. Belley-Cote EP, Hanif H, D’Aragon F, Eikelboom JW, Anderson JL, Borgman M, et al. Genotype-guided versus standard vitamin K antagonist dosing algorithms in patients initiating anticoagulation. A systematic review and meta-analysis. Thromb Haemost. 2015;114:768–77. 10.1160/TH15-01-0071.
  19. Mega JL, Simon T, Collet JP, Anderson JL, Antman EM, Bliden K, et al. Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA. 2010;304:1821–30. 10.1001/jama.2010.1543.
  20. Fontana P, Cattaneo M, Combescure C, Reny JL. Tailored Thienopyridine therapy: no urgency for CYP2C19 genotyping. J Am Heart Assoc. 2013;2:e000131. 10.1161/JAHA.112.000131.

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