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      Combined oral contraceptives: venous thrombosis

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          Abstract

          Combined oral contraceptive (COC) use has been associated with venous thrombosis (VT) (i.e., deep venous thrombosis and pulmonary embolism). The VT risk has been evaluated for many estrogen doses and progestagen types contained in COC but no comprehensive comparison involving commonly used COC is available.

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          Most cited references 105

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          Incidence and mortality of venous thrombosis: a population-based study.

          Estimates of the incidence of venous thrombosis (VT) vary, and data on mortality are limited. We estimated the incidence and mortality of a first VT event in a general population. From the residents of Nord-Trøndelag county in Norway aged 20 years and older (n = 94 194), we identified all cases with an objectively verified diagnosis of VT that occurred between 1995 and 2001. Patients and diagnosis characteristics were retrieved from medical records. Seven hundred and forty patients were identified with a first diagnosis of VT during 516,405 person-years of follow-up. The incidence rate for all first VT events was 1.43 per 1000 person-years [95% confidence interval (CI): 1.33-1.54], that for deep-vein thrombosis (DVT) was 0.93 per 1000 person-years (95% CI: 0.85-1.02), and that for pulmonary embolism (PE) was 0.50 per 1000 person-years (95% CI: 0.44-0.56). The incidence rates increased exponentially with age, and were slightly higher in women than in men. The 30-day case-fatality rate was higher in patients with PE than in those with DVT [9.7% vs. 4.6%, risk ratio 2.1 (95% CI: 1.2-3.7)]; it was also higher in patients with cancer than in patients without cancer [19.1% vs. 3.6%, risk ratio 3.8 (95% CI 1.6-9.2)]. The risk of dying was highest in the first months subsequent to the VT, after which it gradually approached the mortality rate in the general population. This study provides estimates of incidence and mortality of a first VT event in the general population.
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            Natural history of venous thromboembolism.

             Clive Kearon (2003)
            Most deep vein thromboses (DVTs) start in the calf, and most probably resolve spontaneously. Thrombi that remain confined to the calf rarely cause leg symptoms or symptomatic pulmonary embolism (PE). The probability that calf DVT will extend to involve the proximal veins and subsequently cause PE increases with the severity of the initiating prothrombotic stimulus. Although acute venous thromboembolism (VTE) usually presents with either leg or pulmonary symptoms, most patients have thrombosis at both sites at the time of diagnosis. Proximal DVTs resolve slowly during treatment with anticoagulants, and thrombi remain detectable in half of the patients after a year. Resolution of DVT is less likely in patients with a large initial thrombus or cancer. About 10% of patients with symptomatic DVTs develop severe post-thrombotic syndrome within 5 years, and recurrent ipsilateral DVT increases this risk. About 10% of PEs are rapidly fatal, and an additional 5% cause death later, despite diagnosis and treatment. About 50% of diagnosed PEs are associated with right ventricular dysfunction, which is associated with a approximately 5-fold greater in-hospital mortality. There is approximately 50% resolution of PE after 1 month of treatment, and perfusion eventually returns to normal in two thirds of patients. About 5% of treated patients with PE develop pulmonary hypertension as a result of poor resolution. After a course of treatment, the risk of recurrent thrombosis is higher (ie, approximately 10% per patient-year) in patients without reversible risk factors, in those with cancer, and in those with prothrombotic biochemical abnormalities such as antiphospholipid antibodies and homozygous factor V Leiden.
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              Hormonal contraception and risk of venous thromboembolism: national follow-up study

              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 ( 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 μg 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.
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                Author and article information

                Journal
                Cochrane Database of Systematic Reviews
                Wiley
                14651858
                March 03 2014
                Affiliations
                [1 ]Instituto Previdencia dos Servidores do Estado de Minas Gerais; Minas Gerais Brazil
                [2 ]University College London; Department of Epidemiology and Public Health; London UK
                [3 ]Leiden University Medical Center; Epidemiology; PO Box 9600 Leiden Netherlands 2300RC
                [4 ]Leiden University Medical Center; Department of Clinical Epidemiology; PO Box 9600 Leiden Netherlands 2300RC
                [5 ]Leiden University Medical Center; Department of Gynaecology, Division of Reproductive Medicine and Dept. of Clinical Epidemiology; PO Box 9600 Albinusdreef 2 Leiden Netherlands NL 2300 RC
                [6 ]Leiden University Medical Center; Department of Medical Statistics; PO Box 9600 Leiden Netherlands 2300 RC
                Article
                10.1002/14651858.CD010813.pub2
                24590565
                © 2014
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