Uzun Dönem Kontrasepsiyonda Risk Var mıdır? Contraception Contraception June 2008 June 2008 Uzun Dönem Kontrasepsiyonda Risk Var mıdır? Mustafa Uğur Zekai Tahir Burak Hastanesi, Ankara, Türkiye National Prescribing Centre National Prescribing Centre 1

Contraception June 2008 National Prescribing Centre

Suçlu Kim? Verilen endikasyon doğru muydu? Şeker gibi dağıtıyor muyuz? Contraception June 2008 Suçlu Kim? Verilen endikasyon doğru muydu? Şeker gibi dağıtıyor muyuz? Hasta, olabilecek komplikasyonlar konusunda bilgilendirildi mi? Risk araştırması (trombofili) yapılmalı mıydı? Onam formu alınmalı mıydı? İlaç firması sorumlu mudur? Bu durum tıbbi bir hata(malpractice)mıdır? National Prescribing Centre

Contraception June 2008 Expectant management of functional ovarian cysts: an alternative to hormonal therapy. Fonksiyonel over kistlerinde düşük-doz monofazik, yüksek-doz monofazik, multifazik OKS ile tedavi ve beklentisel yaklaşım arasında fark yok. Turan C., Zorlu CG, Ugur M, Ozcan T, Kaleli B, Gokmen O. Int J Gynaecol Obstet,1994 National Prescribing Centre

Hormonal Kontrasepsiyonda Riskler Contraception June 2008 Hormonal Kontrasepsiyonda Riskler Venöz Tromboemboli (VTE) Arteryel tromboz (MI) İnme (stroke) Safra kesesi hastalıkları Karbonhidrat metabolizması değişiklikleri Kanser riskinde artış (meme, serviks, karaciğer) Kilo alımı Yüzde kloazma Seksüel disfonksiyon Hipertansiyon National Prescribing Centre

OKS Koagulasyon Sistemi Contraception June 2008 OKS Koagulasyon Sistemi EE Faktör V, VIII, X, Fibrinojen Estrojen dozu ile ilişkili (50>35 µgr) Risk, yaş ve VKİ ile artar. Sigara kullanımı VTE de etkin değil. National Prescribing Centre

OKS Venöz Tromboemboli Contraception June 2008 OKS Venöz Tromboemboli Kullananlarda 3-4 kat daha fazla risk Desogestrel , CPA, gestoden, drosperinon ile daha fazla risk (?) Trombofili varlığında çok artmış risk Risk artışı 4.aydan itibaren ilk yılda belirgin sonra azalıyor. National Prescribing Centre

Contraception June 2008 Hormonal contraception and risk of venous thromboembolism: national follow-up study. Study Healthy Danish women 15-49 years, from 1995-2005, 10.4 M woman –years BMJ. 2009 Aug 13;339:b2890. doi: 10.1136/bmj.b2890. Hormonal contraception and risk of venous thromboembolism: national follow-up study. Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Gynaecological Clinic, Rigshospitalet, Copenhagen University, DK-2100 Copenhagen, Denmark. Lidegaard@rh.regionh.dk Comment in: BMJ. 2009;339:b3164. OBJECTIVE: To assess the risk of venous thrombosis in current users of different types of hormonal contraception, focusing on regimen, oestrogen dose, type of progestogen, and route of administration. DESIGN: National cohort study. SETTING: Denmark, 1995-2005. PARTICIPANTS: Danish women aged 15-49 with no history of cardiovascular or malignant disease. MAIN OUTCOME MEASURES: Adjusted rate ratios for all first time deep venous thrombosis, portal thrombosis, thrombosis of caval vein, thrombosis of renal vein, unspecified deep vein thrombosis, and pulmonary embolism during the study period. RESULTS: 10.4 million woman years were recorded, 3.3 million woman years in receipt of oral contraceptives. In total, 4213 venous thrombotic events were observed, 2045 in current users of oral contraceptives. The overall absolute risk of venous thrombosis per 10 000 woman years in non-users of oral contraceptives was 3.01 and in current users was 6.29. Compared with non-users of combined oral contraceptives the rate ratio of venous thrombembolism in current users decreased with duration of use (<1 year 4.17, 95% confidence interval 3.73 to 4.66, 1-4 years 2.98, 2.73 to 3.26, and >4 years 2.76, 2.53 to 3.02; P<0.001) and with decreasing dose of oestrogen. Compared with oral contraceptives containing levonorgestrel and with the same dose of oestrogen and length of use, the rate ratio for oral contraceptives with norethisterone was 0.98 (0.71 to 1.37), with norgestimate 1.19 (0.96 to 1.47), with desogestrel 1.82 (1.49 to 2.22), with gestodene 1.86 (1.59 to 2.18), with drospirenone 1.64 (1.27 to 2.10), and with cyproterone 1.88 (1.47 to 2.42). Compared with non-users of oral contraceptives, the rate ratio for venous thromboembolism in users of progestogen only oral contraceptives with levonorgestrel or norethisterone was 0.59 (0.33 to 1.03) or with 75 mug desogestrel was 1.12 (0.36 to 3.49), and for hormone releasing intrauterine devices was 0.90 (0.64 to 1.26). CONCLUSION: The risk of venous thrombosis in current users of combined oral contraceptives decreases with duration of use and decreasing oestrogen dose. For the same dose of oestrogen and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestogen only pills and hormone releasing intrauterine devices were not associated with any increased risk of venous thrombosis. OR 2.03 (1.91 to 2.16) RR 1.54 (1.48 to 1.58) Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C., BMJ. 2009 Aug 13;339:b2890. doi: 10.1136/bmj.b2890. National Prescribing Centre 8

Contraception June 2008 Hormonal contraception and risk of venous thromboembolism: national follow-up study. Study Healthy Danish women 15-49 years, from 1995-2005, 10.4 M woman –years BMJ. 2009 Aug 13;339:b2890. doi: 10.1136/bmj.b2890. Hormonal contraception and risk of venous thromboembolism: national follow-up study. Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Gynaecological Clinic, Rigshospitalet, Copenhagen University, DK-2100 Copenhagen, Denmark. Lidegaard@rh.regionh.dk Comment in: BMJ. 2009;339:b3164. OBJECTIVE: To assess the risk of venous thrombosis in current users of different types of hormonal contraception, focusing on regimen, oestrogen dose, type of progestogen, and route of administration. DESIGN: National cohort study. SETTING: Denmark, 1995-2005. PARTICIPANTS: Danish women aged 15-49 with no history of cardiovascular or malignant disease. MAIN OUTCOME MEASURES: Adjusted rate ratios for all first time deep venous thrombosis, portal thrombosis, thrombosis of caval vein, thrombosis of renal vein, unspecified deep vein thrombosis, and pulmonary embolism during the study period. RESULTS: 10.4 million woman years were recorded, 3.3 million woman years in receipt of oral contraceptives. In total, 4213 venous thrombotic events were observed, 2045 in current users of oral contraceptives. The overall absolute risk of venous thrombosis per 10 000 woman years in non-users of oral contraceptives was 3.01 and in current users was 6.29. Compared with non-users of combined oral contraceptives the rate ratio of venous thrombembolism in current users decreased with duration of use (<1 year 4.17, 95% confidence interval 3.73 to 4.66, 1-4 years 2.98, 2.73 to 3.26, and >4 years 2.76, 2.53 to 3.02; P<0.001) and with decreasing dose of oestrogen. Compared with oral contraceptives containing levonorgestrel and with the same dose of oestrogen and length of use, the rate ratio for oral contraceptives with norethisterone was 0.98 (0.71 to 1.37), with norgestimate 1.19 (0.96 to 1.47), with desogestrel 1.82 (1.49 to 2.22), with gestodene 1.86 (1.59 to 2.18), with drospirenone 1.64 (1.27 to 2.10), and with cyproterone 1.88 (1.47 to 2.42). Compared with non-users of oral contraceptives, the rate ratio for venous thromboembolism in users of progestogen only oral contraceptives with levonorgestrel or norethisterone was 0.59 (0.33 to 1.03) or with 75 mug desogestrel was 1.12 (0.36 to 3.49), and for hormone releasing intrauterine devices was 0.90 (0.64 to 1.26). CONCLUSION: The risk of venous thrombosis in current users of combined oral contraceptives decreases with duration of use and decreasing oestrogen dose. For the same dose of oestrogen and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestogen only pills and hormone releasing intrauterine devices were not associated with any increased risk of venous thrombosis. OR 2.03 (1.91 to 2.16) RR 1.54 (1.48 to 1.58) Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C., BMJ. 2009 Aug 13;339 National Prescribing Centre 9

Contraception June 2008 Hormonal contraception and risk of venous thromboembolism: national follow-up study. Study Healthy Danish women 15-49 years, from 1995-2005, 10.4 M woman –years BMJ. 2009 Aug 13;339:b2890. doi: 10.1136/bmj.b2890. Hormonal contraception and risk of venous thromboembolism: national follow-up study. Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C. Gynaecological Clinic, Rigshospitalet, Copenhagen University, DK-2100 Copenhagen, Denmark. Lidegaard@rh.regionh.dk Comment in: BMJ. 2009;339:b3164. OBJECTIVE: To assess the risk of venous thrombosis in current users of different types of hormonal contraception, focusing on regimen, oestrogen dose, type of progestogen, and route of administration. DESIGN: National cohort study. SETTING: Denmark, 1995-2005. PARTICIPANTS: Danish women aged 15-49 with no history of cardiovascular or malignant disease. MAIN OUTCOME MEASURES: Adjusted rate ratios for all first time deep venous thrombosis, portal thrombosis, thrombosis of caval vein, thrombosis of renal vein, unspecified deep vein thrombosis, and pulmonary embolism during the study period. RESULTS: 10.4 million woman years were recorded, 3.3 million woman years in receipt of oral contraceptives. In total, 4213 venous thrombotic events were observed, 2045 in current users of oral contraceptives. The overall absolute risk of venous thrombosis per 10 000 woman years in non-users of oral contraceptives was 3.01 and in current users was 6.29. Compared with non-users of combined oral contraceptives the rate ratio of venous thrombembolism in current users decreased with duration of use (<1 year 4.17, 95% confidence interval 3.73 to 4.66, 1-4 years 2.98, 2.73 to 3.26, and >4 years 2.76, 2.53 to 3.02; P<0.001) and with decreasing dose of oestrogen. Compared with oral contraceptives containing levonorgestrel and with the same dose of oestrogen and length of use, the rate ratio for oral contraceptives with norethisterone was 0.98 (0.71 to 1.37), with norgestimate 1.19 (0.96 to 1.47), with desogestrel 1.82 (1.49 to 2.22), with gestodene 1.86 (1.59 to 2.18), with drospirenone 1.64 (1.27 to 2.10), and with cyproterone 1.88 (1.47 to 2.42). Compared with non-users of oral contraceptives, the rate ratio for venous thromboembolism in users of progestogen only oral contraceptives with levonorgestrel or norethisterone was 0.59 (0.33 to 1.03) or with 75 mug desogestrel was 1.12 (0.36 to 3.49), and for hormone releasing intrauterine devices was 0.90 (0.64 to 1.26). CONCLUSION: The risk of venous thrombosis in current users of combined oral contraceptives decreases with duration of use and decreasing oestrogen dose. For the same dose of oestrogen and the same length of use, oral contraceptives with desogestrel, gestodene, or drospirenone were associated with a significantly higher risk of venous thrombosis than oral contraceptives with levonorgestrel. Progestogen only pills and hormone releasing intrauterine devices were not associated with any increased risk of venous thrombosis. OR 2.03 (1.91 to 2.16) RR 1.54 (1.48 to 1.58) Lidegaard Ø, Løkkegaard E, Svendsen AL, Agger C., BMJ. 2009 Aug 13;339 National Prescribing Centre 10

Contraception June 2008 MEGA: Venous thromboembolism increased with OC use irrespective of progestin type Study 1524 Premenopausal women <50 years old vs 1760 controls MEGA study: multiple environmental and genetic assessment of risk factors for venous thrombosis-study. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. van Hylckama Vlieg A, Helmerhorst FM, Vandenbroucke JP, Doggen CJ, Rosendaal FR. BMJ. 2009 Aug 13;339:b2921. doi: 10.1136/bmj.b2921. Department of Clinical Epidemiology, Leiden University Medical Center, C7- P, PO Box 9600, NL-2300 RC Leiden, Netherlands. OBJECTIVE: To assess the thrombotic risk associated with oral contraceptive use with a focus on dose of oestrogen and type of progestogen of oral contraceptives available in the Netherlands. DESIGN: Population based case-control study. SETTING: Six participating anticoagulation clinics in the Netherlands (Amersfoort, Amsterdam, The Hague, Leiden, Rotterdam, and Utrecht). PARTICIPANTS: Premenopausal women <50 years old who were not pregnant, not within four weeks postpartum, and not using a hormone excreting intrauterine device or depot contraceptive. Analysis included 1524 patients and 1760 controls. MAIN OUTCOME MEASURES: First objectively diagnosed episodes of deep venous thrombosis of the leg or pulmonary embolism. Odds ratios calculated by cross-tabulation with a 95% confidence interval according to Woolf's method; adjusted odds ratios estimated by unconditional logistic regression, standard errors derived from the model. RESULTS: Currently available oral contraceptives increased the risk of venous thrombosis fivefold compared with non-use (odds ratio 5.0, 95% CI 4.2 to 5.8). The risk clearly differed by type of progestogen and dose of oestrogen. The use of oral contraceptives containing levonorgestrel was associated with an almost fourfold increased risk of venous thrombosis (odds ratio 3.6, 2.9 to 4.6) relative to non-users, whereas the risk of venous thrombosis compared with non-use was increased 5.6-fold for gestodene (5.6, 3.7 to 8.4), 7.3-fold for desogestrel (7.3, 5.3 to 10.0), 6.8-fold for cyproterone acetate (6.8, 4.7 to 10.0), and 6.3-fold for drospirenone (6.3, 2.9 to 13.7). The risk of venous thrombosis was positively associated with oestrogen dose. We confirmed a high risk of venous thrombosis during the first months of oral contraceptive use irrespective of the type of oral contraceptives. CONCLUSIONS: Currently available oral contraceptives still have a major impact on thrombosis occurrence and many women do not use the safest brands with regard to risk of venous thrombosis. van Hylckama Vlieg A, et al. BMJ. 2009 Aug 13;339:b2921. doi:0.1136/bmj.b2921. National Prescribing Centre 11

Risk of venous thromboembolism* by population characteristics Contraception June 2008 Risk of venous thromboembolism* by population characteristics *Cases of non-fatal venous thromboembolism. Food and Drug Administration, Oral contraceptives and risk of blood clots. FDA Talk Papers, Nov. 14, 1995. Ethnic distribution of factor V Leiden in 4047 men and women. Implications for venous thromboembolism screening. Ridker PM, Miletich JP, Hennekens CH, Buring JE. JAMA. 1997 Apr 23-30;277(16):1305-7. Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA 02215-1204, USA. pmridker@bics.bwh.harvard.edu OBJECTIVE: To estimate ethnic-specific prevalence rates of factor V Leiden, an inherited defect of hemostasis associated with risk of venous thrombosis. DESIGN: Survey of 4047 American men and women participating in the Physicians' Health Study (PHS) or in the Women's Health Study (WHS). All study participants were free of myocardial infarction, stroke, or venous thrombosis. MAIN OUTCOME MEASURE: Prevalence of G1691A Leiden mutation in the gene coding for coagulation factor V was determined in the PHS group using polymerase chain reaction techniques and, in the WHS group, a second-generation activated protein C (APC)-resistance screening test with genetic confirmation of all borderline and low-value results. RESULTS: In 2468 Caucasian Americans, carrier frequency of factor V Leiden was 5.27% (95% confidence interval [CI], 4.42%-6.22%). Carrier frequency was 2.21% in 407 Hispanic Americans, 1.23% in 650 African Americans, 0.45% in 442 Asian Americans, and 1.25% in 80 Native Americans. Thus, prevalence of factor V Leiden was less among minority subjects (P=.001). Carrier frequencies were similar in Caucasian men and women (5.53% vs 4.85% respectively, P=.5). CONCLUSION: These data indicate that prevalence of factor V Leiden is greater among Caucasians than minority Americans. These data have implications for clinicians considering whether to screen for factor V Leiden in high-risk groups such as those with prior venous thromboses or coexistent defects of anticoagulation and women at risk for postpartum thrombosis or seeking oral contraceptives. FDA. FDA Talk Paper. 1995. Ridker PM, et al. JAMA. 1997 Apr 23-30;277(16):1305-7. National Prescribing Centre 12

Rutin Trombofili Araştırması Yapalım mı? Contraception June 2008 Rutin Trombofili Araştırması Yapalım mı? Anamnez ve aile öyküsü olanlarda trombofili araştıralım. Olmayanlarda araştırma yapmak ekonomik değil. Kullanırken VTE olursa trombofili araştıralım WHO Contraceptive Technology Update, 2004 National Prescribing Centre

OKS Arteriyel Tromboz (MI) Contraception June 2008 OKS Arteriyel Tromboz (MI) Estrojen dozu önemli, progesteronlar arasında fark yok 50 µg EE, 35 yaş üzeri, risk faktörü varlığında MI riskinde artış. Yaş, sigara içimi, VKI eşitlendiğinde OKS kullanımı riski artırmıyor. OR=1.14 (CI=0.24-4.72) Sidney, 1998 Önceki kullanıcılarda risk artışı yok National Prescribing Centre

Risk of myocardial infarction in current OC users by smoking status Contraception June 2008 Risk of myocardial infarction in current OC users by smoking status Heavy smokers defined as: *10 cigarettes/day; **15 cigarettes/day; ***25 cigarettes/day. WHO (Europe). 1997* Croft P (RCGP). 1989** Rosenberg L. 1990*** 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. Croft P, Hannaford P. Risk factors for acute myocardial infarction in women: evidence from the Royal College of General Practitioners’ oral contraceptive study. BMJ 1989;298:165-8. Rosenberg L, Palmer J, Lesko S, Shapiro S. Oral contraceptive use and the risk of myocardial infarction. Am J Epidemiol 1990;131:1009-16. Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. [No authors listed] Lancet. 1997 Apr 26;349(9060):1202-9. BACKGROUND: The association between oral contraceptive (OC) use and acute myocardial infarction (AMI) was established in studies from northern Europe and the USA, which took place during the 1960s and 1970s. Few data are available to quantify the risk worldwide of AMI associated with use of OCs introduced since those early studies. This hospital-based case-control study examined the association between a first AMI and current OC use in women from Africa, Asia, Europe, and Latin America (21 centres). METHODS: Cases were women aged 20-44 years who had definite or possible AMI (classified by history, electrocardiographic, and cardiac-enzyme criteria), who were admitted to hospital, and who survived for at least 24 h. Up to three hospital controls matched by 5-year age-band were recruited for each of the 368 cases (941 controls). All participants were interviewed while in hospital with the same questionnaire, which included information on medical and personal history, lifetime contraceptive use, and blood-pressure screening before the most recent episode of OC use. Odds ratios compared the risk of AMI in current OC users and in non-users (past users and never-users combined). FINDINGS: The overall odds ratio for AMI was 5.01 (95% CI 2.54-9.90) in Europe and 4.78 (2.52-9.07) in the non-European (developing) countries; however, these risk estimates reflect the frequent coexistence of other risk factors among OC users who have AMI. Very few AMIs were identified among women who had no cardiovascular risk factors and who reported that their blood pressure had been checked before OC use; odds ratios associated with OC use in such women were not increased in either Europe or the developing countries. Among OC users who smoked ten or more cigarettes per day, the odds ratios in Europe and in the developing countries were over 20. Similarly, among OC users with a history of hypertension (during pregnancy or at any other time), odds ratios were at least ten in both groups of countries. No consistent association between odds ratios for AMI and age of OC users or oestrogen dose was apparent in either group of countries. No significant increase in odds ratios was apparent with increasing duration of OC use among current users, and odds ratios were not significantly increased in women who had stopped using OCs, even after long exposure. The study had insufficient power to examine whether progestagen dose or type had any effect on AMI risk. INTERPRETATION: Current use of combined OCs is associated with an increased risk of AMI among women with known cardiovascular risk factors and among those who have not been effectively screened, particularly for blood pressure. AMI is extremely rare in younger (< 35 years) non-smoking women who use OCs, and the estimated excess risk of AMI in such women in the European centres is about 3 per 10(6) woman-years. The risk is likely to be even lower if blood pressure is screened before, and presumably during, OC use. Only among older women who smoke is the degree of excess risk associated with OCs substantial (about 400 per 10(6) woman-years). Risk factors for acute myocardial infarction in women: evidence from the Royal College of General Practitioners' oral contraception study. Croft P, Hannaford PC. BMJ. 1989 Jan 21;298(6667):165-8. Industrial and Community Health Research Centre, Medical Institute, Hartshill, Stoke on Trent. To determine the pattern of risk factors for acute myocardial infarction associated solely with women a nested case-control study was carried out on cohort data collected during the Royal College of General Practitioners' oral contraception study. Smoking (adjusted relative risk 1.7 for light smokers and 4.3 for heavy smokers), hypertension (2.4), toxaemia of pregnancy (2.8), and diabetes mellitus (6.9) were associated with a significantly increased risk of myocardial infarction. There was no significant trend of risk with social class. Current use of the pill increased the risk only among women who also smoked (relative risk 20.8 for heavy smokers). Previous use of the pill did not influence the risk of myocardial infarction. If heavy smokers also had a history of toxaemia of pregnancy their risk of myocardial infarction was further increased (relative risk 41.0). Other variables associated solely with women, such as parity, hysterectomy, and hormone replacement therapy, had little effect on the risk of having a myocardial infarction. Overall, smoking was the most important independent risk factor and had a strong influence on risks associated with other factors. Oral contraceptive use and the risk of myocardial infarction. Rosenberg L, Palmer JR, Lesko SM, Shapiro S. Am J Epidemiol. 1990 Jun;131(6):1009-16. Slone Epidemiology Unit, Boston University School of Medicine, Brookline, MA 02146. The relation of oral contraceptive use to the risk of myocardial infarction was assessed in a hospital-based case-control study of women aged 25-64 years conducted from 1985 to 1988 in New England; 910 women with first myocardial infarctions were compared with 1,760 control women. Oral contraceptive use, after discontinuation, was not associated with an increased risk of myocardial infarction, whether use had ceased in the distant past or more recently. The overall relative risk estimate for women who had used oral contraceptives in the past for at least 5 years compared with nonusers was 1.1 (95% confidence interval 0.8-1.5) after allowance for confounding factors. Past use was not associated with risk in any age group, in subgroups of women with predisposing factors, or in women at low risk because of the absence of predisposing factors. The results suggest that long-term oral contraceptive use, after discontinuation, does not influence the risk of myocardial infarction. There were few current users and the results for current use were inconclusive: for premenopausal women who had used oral contraceptives in the previous month relative to those who had not, the age-adjusted relative risk estimate was 1.1 (95% confidence interval 0.4-3.1). WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet 1997 Apr 26;349(9060):1202-9. Croft P, Hannaford P. BMJ. 1989 Jan;298(6667):165-8. Rosenberg L, et al. Am J Epidemiol 1990 Jun;131(6):1009-16. National Prescribing Centre 15

Contraception June 2008 OKS ve İnme (Stroke) Uzun süreli ve daha önceki kullanımda risk artışı yok Hipertansiyon ve sigara kullanımında belirgin risk artışı. Migren inme riski için bağımsız risk faktörü. Migrende Aura semptomları varsa riskte belirgin artış National Prescribing Centre

Migren İnme ve OKS Kullanımı Contraception June 2008 Migren İnme ve OKS Kullanımı Genç kadınlarda oluşabilecek absolut risk 6 / 100,000 ♀ / yıl – sağlıklı 12 / 100,000 ♀ / yıl – migren 18 / 100,000 ♀ / yıl – aura ile migren 12 / 100,000 ♀ / yıl – sağlıklı OKS kullanan 19 / 100,000 ♀ / yıl – migren OKS kullanan 30 / 100,000 ♀ / yıl – aura ile migren OKS 34 / 100,000 ♀ / yıl – gebelikte inme Gillum et al,JAMA 2000 National Prescribing Centre

OKS Meme Kanseri Halen kullananlarda minimal bir risk artışı var. Contraception Contraception June 2008 June 2008 OKS Meme Kanseri Halen kullananlarda minimal bir risk artışı var. Kestikten sonra risk azalıyor. 10 yıl sonra kalkıyor. Kullanan hastalardaki meme ca. daha az metastatik. Aile öyküsünde meme kanseri olanlarda risk artışı yok. BRCA1, BRCA2 mutasyonu taşıyanlarda risk artışı var. National Prescribing Centre National Prescribing Centre 19

OKS Servikal Kanser Epidemiolojik çalışmalarda minimal risk artışı. Contraception June 2008 OKS Servikal Kanser Epidemiolojik çalışmalarda minimal risk artışı. HPV riski artıran kofaktör. Risk kullanım süresi ile artar. National Prescribing Centre

Oral Kontraseptif ve Serviks Kanseri HPV E6 E7 Seks Steroid hormonlar p53 Rb

OCP use and Cervical Cancer Contraception June 2008 OCP use and Cervical Cancer Study Meta-Analysis: 28 studies, 12531 cases 146 Lancet. 2003 Apr 5;361(9364):1159-67. Cervical cancer and use of hormonal contraceptives: a systematic review. Smith JS, Green J, Berrington de Gonzalez A, Appleby P, Peto J, Plummer M, Franceschi S, Beral V. International Agency for Research on Cancer, Lyon, France. Comment in: Lancet. 2003 May 31;361(9372):1915. BACKGROUND: Human papillomavirus (HPV) is believed to be the most important cause of cervical cancer. Recent studies suggest that long duration use of oral contraceptives increases the risk of cervical cancer in HPV positive women. METHODS: Results from published studies were combined to examine the relationship between invasive and in situ cervical cancer and duration and recency of use of hormonal contraceptives, with particular attention to HPV infection. FINDINGS: 28 eligible studies were identified, together including 12531 women with cervical cancer. Compared with never users of oral contraceptives, the relative risks of cervical cancer increased with increasing duration of use: for durations of approximately less than 5 years, 5-9 years, and 10 or more years, respectively, the summary relative risks were 1.1 (95% CI 1.1-1.2), 1.6 (1.4-1.7), and 2.2 (1.9-2.4) for all women; and 0.9 (0.7-1.2), 1.3 (1.0-1.9), and 2.5 (1.6-3.9) for HPV positive women. The results were broadly similar for invasive and in situ cervical cancers, for squamous cell and adenocarcinoma, and in studies that adjusted for HPV status, number of sexual partners, cervical screening, smoking, or use of barrier contraceptives. The limited available data suggest that the relative risk of cervical cancer may decrease after use of oral contraceptives ceases. However, study designs varied and there was some heterogeneity between study results. INTERPRETATION: Although long duration use of hormonal contraceptives is associated with an increased risk of cervical cancer, the public health implications of these findings depend largely on the extent to which the observed associations remain long after use of hormonal contraceptives has ceased, and this cannot be evaluated properly from published data. 147 Contraception. 2004 May;69(5):347-51. Oral contraceptives and cervical cancer: critique of a recent review. Miller K, Blumenthal P, Blanchard K. Ibis Reproductive Health, 2 Brattle Square, Cambridge, MA 02138, USA. kmiller@ibisreproductivehealth.org A recent review article by Smith et al. in The Lancet purports to find a causal relationship between long- term use of oral contraceptives (OCs) and cervical cancer. While we endorse the search for such a relationship, we felt it important to critically examine Smith et al.'s review process and, as a result, we have questions about the validity of their conclusions. In our view, the findings of published articles as presented by Smith et al. do not confirm a causal connection between long-term use of OCs and cervical cancer. Our goal is not to conduct another formal review of the evidence, but to evaluate whether Smith et al. have met the burden of proof for establishing a causal relationship. Given the importance of OCs to women the world over, we urge reproductive health professionals to consider this issue carefully before accepting that a causal relationship exists. PMID: 15105055 [PubMed - indexed for MEDLINE] Smith JS, et al,, Lancet. 2003 Apr 5;361(9364):1159-67. National Prescribing Centre 22

OCP use and Cervical Cancer: HPV POSITIVE Contraception June 2008 OCP use and Cervical Cancer: HPV POSITIVE Study Meta-Analysis: 28 studies, 12531 cases 146 Lancet. 2003 Apr 5;361(9364):1159-67. Cervical cancer and use of hormonal contraceptives: a systematic review. Smith JS, Green J, Berrington de Gonzalez A, Appleby P, Peto J, Plummer M, Franceschi S, Beral V. International Agency for Research on Cancer, Lyon, France. Comment in: Lancet. 2003 May 31;361(9372):1915. BACKGROUND: Human papillomavirus (HPV) is believed to be the most important cause of cervical cancer. Recent studies suggest that long duration use of oral contraceptives increases the risk of cervical cancer in HPV positive women. METHODS: Results from published studies were combined to examine the relationship between invasive and in situ cervical cancer and duration and recency of use of hormonal contraceptives, with particular attention to HPV infection. FINDINGS: 28 eligible studies were identified, together including 12531 women with cervical cancer. Compared with never users of oral contraceptives, the relative risks of cervical cancer increased with increasing duration of use: for durations of approximately less than 5 years, 5-9 years, and 10 or more years, respectively, the summary relative risks were 1.1 (95% CI 1.1-1.2), 1.6 (1.4-1.7), and 2.2 (1.9-2.4) for all women; and 0.9 (0.7-1.2), 1.3 (1.0-1.9), and 2.5 (1.6-3.9) for HPV positive women. The results were broadly similar for invasive and in situ cervical cancers, for squamous cell and adenocarcinoma, and in studies that adjusted for HPV status, number of sexual partners, cervical screening, smoking, or use of barrier contraceptives. The limited available data suggest that the relative risk of cervical cancer may decrease after use of oral contraceptives ceases. However, study designs varied and there was some heterogeneity between study results. INTERPRETATION: Although long duration use of hormonal contraceptives is associated with an increased risk of cervical cancer, the public health implications of these findings depend largely on the extent to which the observed associations remain long after use of hormonal contraceptives has ceased, and this cannot be evaluated properly from published data. 147 Contraception. 2004 May;69(5):347-51. Oral contraceptives and cervical cancer: critique of a recent review. Miller K, Blumenthal P, Blanchard K. Ibis Reproductive Health, 2 Brattle Square, Cambridge, MA 02138, USA. kmiller@ibisreproductivehealth.org A recent review article by Smith et al. in The Lancet purports to find a causal relationship between long- term use of oral contraceptives (OCs) and cervical cancer. While we endorse the search for such a relationship, we felt it important to critically examine Smith et al.'s review process and, as a result, we have questions about the validity of their conclusions. In our view, the findings of published articles as presented by Smith et al. do not confirm a causal connection between long-term use of OCs and cervical cancer. Our goal is not to conduct another formal review of the evidence, but to evaluate whether Smith et al. have met the burden of proof for establishing a causal relationship. Given the importance of OCs to women the world over, we urge reproductive health professionals to consider this issue carefully before accepting that a causal relationship exists. PMID: 15105055 [PubMed - indexed for MEDLINE] Smith JS, et al,, Lancet. 2003 Apr 5;361(9364):1159-67. National Prescribing Centre 23

OKS Kloazma Yapar mı? Carruthers R. 1967 British Medical Journal Contraception June 2008 OKS Kloazma Yapar mı? Carruthers R. 1967 British Medical Journal National Prescribing Centre

OKS Seksüel Disfonksiyon Yapar mı? Contraception June 2008 OKS Seksüel Disfonksiyon Yapar mı? National Prescribing Centre

OKS Seksüel Disfonksiyon Yapar mı? Contraception June 2008 OKS Seksüel Disfonksiyon Yapar mı? Hipoaktif seksüel istek disfonksiyonu (HSDD) olan kadınların OKS kullananlarında daha düşük testosteron ve yüksek SHBG seviyleri Warnock 2006 J. Sex Med. Anti-androjenik OKS Kullanımı varsa androjenik progestagene değiştirilebilir. National Prescribing Centre

OKS-Karşılaştırmalı etkiler Contraception OKS-Karşılaştırmalı etkiler 30/09/11 June 2008 Progestogenik Androgenik Antiandrogenik Antimineralokortikoid Glukokortikoid etki etki etki etki etki Progesteron + – (+) + – Drospirenon + – + + – Siproteron asetat + – + – (+) Desogestrel + (+) – – – Dienogest + – + – – Gestoden + (+) – (+) – Levonorgestrel + (+) – – – Norgestimate + (+) – – – + etki; (+) terapötik dozlarda ihmal edilebilir; – etkisiz National Prescribing Centre 27

OKS Kilo alımına neden olur mu? Contraception Contraception June 2008 June 2008 OKS Kilo alımına neden olur mu? Progesteron anabolizan etki EE Na ve su tutulumu, iştah artımı 44 çalışmanın meta analizinde (3’ünde plasebo var) OKS ile kilo alımı arasında sebep sonuç ilişkisi yok. Gallo MF, 2006. Cochrane Systematic Review. National Prescribing Centre National Prescribing Centre 28

Contraception June 2008 National Prescribing Centre

Kontraseptif Metodlarda WHO Sınıflaması Contraception June 2008 Kontraseptif Metodlarda WHO Sınıflaması WHO 1 Metodu kullanabilir. Kullanımda kısıtlama yok. WHO 2 Metodu kullanabilir. Metodun faydası riskinden daha yüksek. WHO 3 Metodu kullanmamalı. Ancak bir doktor veya hemşire metodu kullanmasında yarar görüyorsa kullanabilir. WHO 4 Metod kullanılmamalı. Kabul edilemez bir sağlık riski oluşabilir. National Prescribing Centre 30

Contraception June 2008 National Prescribing Centre

Contraception June 2008 National Prescribing Centre

Contraception June 2008 http://www.who.int/reproductivehealth/publications/family_planning/wheel National Prescribing Centre

Contraception June 2008 http://www.who.int/reproductivehealth/publications/family_planning/wheel National Prescribing Centre

Contraception June 2008 http://www.who.int/reproductivehealth/publications/family_planning/wheel National Prescribing Centre

Contraception June 2008 http://www.who.int/reproductivehealth/publications/family_planning/wheel National Prescribing Centre

Contraception June 2008 http://www.who.int/reproductivehealth/publications/family_planning/wheel National Prescribing Centre

Contraception June 2008 http://www.who.int/reproductivehealth/publications/family_planning/wheel National Prescribing Centre

Hormonal Kontrasepsiyon Değerlendirme Contraception June 2008 Hormonal Kontrasepsiyon Değerlendirme Anamnez (VTE, kanser, migren, safra kesesi-kolestaz) Pelvik muayene, ultrason, smear. AKŞ, AST, ALT, Lipid profili Yan etkiler ve yararlar konusunda bilgilendirme Tehlike işaretleri National Prescribing Centre

Hormonal Kontrasepsiyon Tehlike İşaretleri Contraception June 2008 Hormonal Kontrasepsiyon Tehlike İşaretleri Abdominal pain Chest pain and shortness of breath Headaches Eye problems (blurred vision, flashing light, blindness) Severe leg pain National Prescribing Centre

Sigmund Freud

Hormonal Kontrasepsiyonda Resmin Bütünü Contraception June 2008 Hormonal Kontrasepsiyonda Resmin Bütünü Sıfır risk yok, fayda zarar oranı hesaplanmalı. İstenmeyen bir gebeliğin riskleri çok daha büyük. Hormonal kontraseptifler güvenli yöntemler. Küçük bir grup hastada önemli yan etki oluşturablirler. Kullanım öncesi ve süresince uygun değerlendirme ve takip gerekli. National Prescribing Centre

Contraception June 2008 National Prescribing Centre