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P-piller, HT og apopleksi

P-piller, HT og apopleksi. Øjvind Lidegaard Gynækologisk Klinik 4232 Rigshospitalet U-kursus i cerebrovaskulære sygdomme, 29. November 2006. P-piller, HT og CeVD. Brug af p-piller og HT i Danmark Cerebral trombose - Epidemiologi hos yngre kvinder - Pp og cerebral trombose

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P-piller, HT og apopleksi

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  1. P-piller, HT og apopleksi Øjvind Lidegaard Gynækologisk Klinik 4232 Rigshospitalet U-kursus i cerebrovaskulære sygdomme, 29. November 2006

  2. P-piller, HT og CeVD • Brug af p-piller og HT i Danmark • Cerebral trombose - Epidemiologi hos yngre kvinder - Pp og cerebral trombose - HT og cerebral trombose • Cerebral hæmorrhagi - Epidemiologi hos yngre kvinder - Pp og cerebral hæmorrhagi - HT og cerebral hæmorrhagi U-kursus, 28. november 2006

  3. P-piller, HT og CeVD • Brug af p-piller og HT i Danmark • Cerebral trombose - Epidemiologi hos yngre kvinder - Pp og cerebral trombose - HT og cerebral trombose • Cerebral hæmorrhagi - Epidemiologi hos yngre kvinder - Pp og cerebral hæmorrhagi - HT og cerebral hæmorrhagi U-kursus, 29. november 2006

  4. OC use in Denmark 1966-2005 Per cent Calculated from total sale in DDD/fem pop 15-44 years. Li/05

  5. Nor- Norges- Deso- Estrans EE dose Gestodene gestrel timate gestrel >50mcg EE – – – – – 50mcg EE + + – – – 30-40mcg EE + + + + + 20mcg EE – – – + + POP + + – + – OCs: Generations according tooestrogen dose and progestagen types Generation of progestagen 1. 2. "2". 3. 3. 4. Dros- pirenon – 1st gen – 2nd gen 4th gen 3rd gen – – Li/04

  6. OC types in DK according to estrogen dose during the period 1980-2000 50ug EE 30-40ug EE 20ug EE POP Sale statistics. Dansk Lægemiddelstatistik Li/04

  7. Progestagen types in combinedOCin Denmark 1985-2004 (%) Gest. 20ug Gestodene 30ug Desogestrel 20ug Levonorgestrel Desogestrel 30ug Norgestimate Norethisterone Sale statistics. www.laegemiddelstyrelsen.dk Li/05

  8. Use of oral contraceptives in DK 2003DDD/100 women/day at different ages www.laegemiddelstyrelsen.dk Li/05

  9. Brug af p-piller i Danmark Ud af alle kvinder benytter • i gennemsnit 33% i alderen 15-44 år p-piller • mere end hver anden i alderen 20-25 år pp Blandt kvinder, som benytter p-piller bruger • 70% p-piller med 30-40ug østrogen • 2/3 p-piler med 3. el 4. generations gestagen • 90% 2., 3. eller 4. generations p-piller • 1% minipiller

  10. HT sale DK 2002. DDD/1,000 per day www.dachre.dk Danish Sex Hormone Register Study (DaHORS).

  11. HT sale DK 2004. DDD/1,000 per day www.dachre.dk Danish Sex Hormone Register Study (DaHORS).

  12. P-piller, HT og CeVD • Brug af p-piller og HT i Danmark • Cerebral trombose - Epidemiologi hos yngre kvinder - Pp og cerebral trombose - HT og cerebral trombose • Cerebral hæmorrhagi - Epidemiologi hos yngre kvinder - Pp og cerebral hæmorrhagi - HT og cerebral hæmorrhagi U-kursus, 29. november 2006

  13. P-piller, HT og CeVD • Brug af p-piller og HT i Danmark • Cerebral trombose - Epidemiologi hos yngre kvinder - Pp og cerebral trombose - HT og cerebral trombose • Cerebral hæmorrhagi - Epidemiologi hos yngre kvinder - Pp og cerebral hæmorrhagi - HT og cerebral hæmorrhagi U-kursus, 29. november 2006

  14. CTA, AMI and VTE in DK 1980-93Pregnant and puerperal women excluded Incidence per 100,000 per year CTA+AMI Venousdiseases Arterialdiseases CTA VTE AMI DVT PE Li/04 Lidegaard Ø. Am J Obstet Gynecol 1998; 179: S62-7.

  15. Thrombotic diseases in young women CTA AMIVTE Incidence/mio 170 62230 Non pregnant 150 60170 Mortality/mio 3152.7 Non pregnant 3 152.3 Case-fatality rate 2.3%25%1.3% Significant disability 30%30% 5% Long-term survival  Lidegaard. Am J Obstet Gynecol 1998; 179: s62-7 Li/04

  16. Risk factors for cardiovascular diseasesin women of reproductive age CTA AMI VTE High age + + + Smoking + + - Hypertension + + - Diabetes + + - Family VTE - – + Family AMI + + - Family CTA + + - BMI >30 - + + Migraine + – - Varicose veins - – + Leiden fact V - – + Lidegaard, Nordisk Medicin 1998; 113: 187-90

  17. VTE: Genetic risk factors Risk factor Prevalence RR Leiden fact V hetero 5% 8 Leiden fact V homoz 0.2% 64 Protein C insufficiency 0.2% 15 Protein S insufficiency <0.1% >10 Antithrombin III insuff. 0.02% 50 Prothrombin 20210A 2% 3 Hyperhomocysteinaemia 3% 3 Høibraaten E. HRT and risk of VTE. Diss. Oslo 2001 Li/04

  18. Incidence rate of VTE among pregnant and puerperal women, DK 1994-96. N=265 Incidence of VTE per 10,000 exposure years Puerperium(n=103) Pregnancy(n=162) Delivery www.lidegaard.dk/Slides Li/04

  19. Cerebral thromboembolic attacks (CTA) in DK,1987-93, women 15-44 years old. Per mio yearsCTA=cerebral thrombosis (CT) + TIA CTA Incidence Deaths CT TCI Li/02 Lidegaard. Am J Obstet Gynecol 1998; 179: S62-7

  20. P-piller, HT og CeVD • Brug af p-piller og HT i Danmark • Cerebral trombose - Epidemiologi hos yngre kvinder - Pp og cerebral trombose - HT og cerebral trombose • Cerebral hæmorrhagi - Epidemiologi hos yngre kvinder - Pp og cerebral hæmorrhagi - HT og cerebral hæmorrhagi U-kursus, 29. november 2006

  21. Cerebral thromboembolism in DKWomen and men 1980-86 Incidence per 100,000/year Lidegaard, Contraception 1996; 52: 85-92

  22. OCs and cerebral thrombosis Cases/ OR Study PDS controls 2nd/3rd WHO 89-93 489/3967 2.7/1.7 Schwartz 91-95 175/1191 1.1 Heinemann 93-96 220/439 2.7/3.4 Lidegaard 94-98 626/4054 2.2/1.4 Lidegaard et al. Contraception 2002; 65: 197-205

  23. CTA: Conclusion • The risk of CTA decreases with decreasing estrogen dose. • OCs with 3rd gen. progestagens confer a significantly lower risk of CTA than OCs with 2nd gen. progestagens.

  24. OCs and thrombosisCurrent status November 2006* CTAAMIVTE 2nd gen: 2.51.5 3.0 3rd gen: 1.5 1.5 4.0

  25. Clinical guidelines When OCs are prescribed • Careful clinical history including risk factors and family disposition • Previous thrombosis: No OCs • Genetic predisposition Risk factor ≥5: No OCs VTE risk factor <5: Careful inform., 2nd gen No risk factors: Any low dose pill Arterial risk factors: 3rd gen. pill www.dsog.dk/guidelines Li/04

  26. Migræne og p-piller Risiko for hjerneblodprop: Relativ risiko Migræne generelt 3 Migræne med aura 6 Migræne uden aura 2 2. Gen. p-pille 2,5 3. Gen. p-pille 1,5 Migræne + 2. Gen p-pille 7,5 Migræne + 3. Gen p-pille 4,5 Konklusion:Ikke p-piller til kvinder med migræne med aura. Ellers 3. generation

  27. Rygning og p-piller Risiko for blodprop: Hjerne Hjerte Rygning under 10/dag 1,0 4 Rygning 10-20/dag 1,5 6 Rygning >20/dag 2,0 8 2. Gen. p-pille 2,5 1,5 3. Gen. p-pille 1,5 1,5 Konklusion:Ikke p-piller til kvinder der ryger over 20 cigaretter dagligt og som er over 35 år.

  28. P-piller, HT og CeVD • Brug af p-piller og HT i Danmark • Cerebral trombose - Epidemiologi hos yngre kvinder - Pp og cerebral trombose - HT og cerebral trombose • Cerebral hæmorrhagi - Epidemiologi hos yngre kvinder - Pp og cerebral hæmorrhagi - HT og cerebral hæmorrhagi U-kursus, 29. november 2006

  29. Womens health initiative (WHI) EPT vs placebo ET vs placebo Age: 50-79 50-79, -uterus Number: 16,608 10,739 Regimen: 0.6mg CEE/MPA 0.6mg CEE Follow up: 5.2 yrs, 6.8 yrs Average age: 63 years 64 years >60 years 66% 70% Hypertension 36% 48% BMI ≥25: 70%, 80% BMI ≥30: 34% 45% Rossouw et al. JAMA 2002; 288: 321-33 & JAMA 2004: 291: 1701

  30. WHI results EPT ET 50-59 • Coronary heart disease 1.3 0.9 0.6 • Stroke 1.4 1.4 1.1 • Venous thromboembolism 2.1 1.3 1.2 • Breast cancer 1.3 0.8 0.7 • Endometrial cancer 0.8 hysterect. • Colorectal cancer 0.6 1.1 0.6 • Hip fracture 0.7 0.6 NA • Vertebral fracture 0.7 0.6 NA • All cause mortality 1.0 1.0 0.7 Rossouw et al. JAMA 2002; 288: 321-33 & 2004: 291: 1701

  31. HT og Cerebral trombose • Hovedparten af observationsstudier har vist en let øget eller uændret risiko for cerebral trombose blandt kvinder, som aktuelt tager hormoner • Nylige randomiserede studier har dog vist en 20-50% øget risiko for stroke blandt ældre hormonbehandlede risikokvinder Konklusion • HT ikke indiceret som profylakse imod stroke/cerebral trombose. • Relativt kontraindiceret til kvinder med tidligere cerebral trombose. Lemaitre et al. Arch Int Med 2002; 162: 1954-60 Li/02

  32. P-piller, HT og CeVD • Brug af p-piller og HT i Danmark • Cerebral trombose - Epidemiologi hos yngre kvinder - Pp og cerebral trombose - HT og cerebral trombose • Cerebral hæmorrhagi - Epidemiologi hos yngre kvinder - Pp og cerebral hæmorrhagi - HT og cerebral hæmorrhagi U-kursus, 29. november 2006

  33. Subarachnoid haemorrhage (SAH) and intracerebral haemorrhage (ICH) in women and men in Denmark 1994-98 Incidence per 100,000/year SAH women: n=2,027 SAH men: n=1,402 ICH women: n=3,709 ICH men: n=4,194 ICH-m ICH-w Only first ever events during the five-year period included SAH-w SAH-m www.lidegaard.dk/slides Li/02

  34. Subarachnoid haemorrhage (SAH) and intracerebral haemorrhage (ICH) in women and men in Denmark 1994-98 Incidence per 100,000/year Li/00 Only first ever events during thefive-year period included

  35. Cerebrovascular diseasesin young women, DK 1987-93 Incidence per 100,000/year CT SAB TIA ICH Lidegaard, CNS Drugs 1997; 1: 1-5. Li/00

  36. P-piller, HT og CeVD • Brug af p-piller og HT i Danmark • Cerebral trombose - Epidemiologi hos yngre kvinder - HT og cerebral trombose - Pp og cerebral trombose • Cerebral hæmorrhagi - Epidemiologi hos yngre kvinder - Pp og cerebral hæmorrhagi - HT og cerebral hæmorrhagi U-kursus, 29. november 2006 Li/04

  37. OCs and cerebral hemorrhage Study Nat PDS Type cas/con RR95% CI Inman UK 76 SAH 134/134 1.50.8-3.0 Thorog. UK 78 SAH 158/304 1.40.9-2.4 RCGP UK 68-90 SAH 73/219 1.50.6-3.7 ICH 22/66 1.10.2-7.1 WHO Eu 89-93 SAH 198/517 1.60.9-2.8 - - ICH 46/120 0.9 0.3-3.0 Schwartz US 91-95 CH 196/831 1.00.5-1.9 Lidegaard DK 97-98 CH 53/590 1.72nd0.9-3.2 1.53rd0.9-2.6 Li/02

  38. OCs and cerebral haemorrhage Incidence per 100,000/year 1 2 3 4 5 6 7 8 1. Petitti Lancet 1978; i: 234-6. 2. Hannaford. Stroke 1994; 25: 935-423: WHO. Lancet 1996; 348: 505-10, 1989-93.4: Petitti. N Engl J Med 1996; 335: 8-15. 1991-94.5: Schwartz, Ann Int Med 1997; 127: 596-603. 6.Poulter Lancet 1999; 354: Li/04 7. Jick, Lancet 1999; 354,8. Lidegaard, unpublished, 2000

  39. Metaanalysis on HT and death OR, 95% CI Aim: HT, deaths, age Meta-analysis on 30 RCT 26,708 participants Salpeter et al. J Gen Intern Med 2004; 19: 791-804

  40. OCs and CH: Conclusion • Overall, no increased risk of intracerebral haemorrhage in current users of low-dose OCs. • No difference in risk of SAB between OCs with 2nd and 3rd gen. progestagens. Li/00

  41. OCs and apoplexyCurrent status November 2006 CTA SAB ICH 2nd gen: 2.5 1.5 1.0 3rd gen: 1.5 1.5 1.0

  42. P-piller, HT og CeVD • Brug af p-piller og HT i Danmark • Cerebral trombose - Epidemiologi hos yngre kvinder - HT og cerebral trombose - Pp og cerebral trombose • Cerebral hæmorrhagi - Epidemiologi hos yngre kvinder - Pp og cerebral hæmorrhagi - HT og cerebral hæmorrhagi U-kursus, 29. november 2006 Li/04

  43. HT and CH: Conclusion • Overall, no increased risk of cerebral haemorrhage in women on HT. • Previous cerebral haemorrhage not a contraindication against HT. Nelson et al. JAMA 2002; 288: 872-81 Li/04

  44. Li/03

  45. Useful links • www.lidegaard.dk/slides • www.dsog.dk/guidelines Li/04

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