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Contraception. 2006 Feb; 73(2):179-188.Women with hypertension are at increased risk for cardiovascular events. Combined oral contraceptive (COC) use, even among low-dose users, has been associated with a small excess risk for cardiovascular events among healthy women. In this systematic review, we examined cardiovascular risks among COC users with hypertension. After searching MEDLINE for all articles published from 1966 through February 2005 relevant to COC use, hypertension and cardiovascular disease, we identified 25 articles for this review. Overall, these studies showed that hypertensive COC users were at higher risk for stroke and acute myocardial infarction (AMI) than hypertensive non-COC users, but that they were not at higher risk for venous thromboembolism (VTE). Women who did not have their blood pressure measured before initiating COC use were at higher risk for ischemic stroke and AMI, but not for hemorrhagic stroke or VTE, than COC users who did not have their blood pressure measured. (author's)
WORLD HEALTH ORGANIZATION TECHNICAL REPORT SERIES.. 1998; (877):v-vii, 1-89.This report presents conclusions and recommendations of the WHO Scientific Group relating to various cardiovascular diseases in women of reproductive age, particularly those using steroid hormone contraception. Chapter 1 presents an introduction on the subject, while chapter 2 describes the epidemiological approaches used to examine the safety of steroid contraceptives and the measurement and interpretation of relative and absolute risks. It also discusses the epidemiological evaluation of the cardiovascular effects of the hormonal contents of combined oral contraceptives (COCs). Chapters 3 to 7 examine data on acute myocardial infarction, ischemic and hemorrhagic stroke, and venous thromboembolism obtained from case-control and cohort studies. Chapter 8 reviews possible biological mechanisms for cardiovascular effects of COCs, including the interplay between glucose and insulin metabolism, lipid and lipoprotein metabolism, the hemostatic system, and blood pressure. Chapter 9 studies the factors which may increase the risk of cardiovascular diseases from COC use and presents a model for assessing the risk of cardiovascular disease among users of COC in different parts of the world. Moreover, this chapter looks at the other considerations concerning the safety of COCs, including the role of screening in reducing the risk of cardiovascular disease, as well the importance of disseminating research findings. This report ends with recommendations for further research.
The use of a large-scale surveillance system in Planned Parenthood Federation of America clinics to monitor cardiovascular events in users of combination oral contraceptives.
International Journal of Fertility and Women's Medicine. 1999 Jan-Feb; 44(1):19-30.In response to studies reporting an excess of thrombotic events in women who used oral contraceptives (OCs) containing third-generation progestins, the Planned Parenthood Federation of America (PPFA) launched a retrospective review of clients at all PPFA-affiliated centers during 1993-95. During the 3-year study period, 2,265,087 woman-years of OC use were recorded in clinic drug sale records. All OCs prescribed in this period contained 30 or 35 mcg of estrogen and either norgestimate (21.0%), desogestrel (8.9%), norethindrone (46.6%), or levonorgestrel (23.6%) as the progestin. 70 major thrombotic events among clients using OCs (3 vascular complications per 100,000 woman-years of OC use) were reported to PPFA's risk management division during 1993-95; these included 25 cases of deep vein thrombosis, 20 cases of pulmonary embolism, 22 cerebrovascular accidents, and 3 myocardial infarctions. There were 5 deaths (0.22/100,000 woman-years of use), all from pulmonary emboli. The thrombotic event rates were calculated as the relative risk of complication, comparing the risk of each event for one progestin relative to the other three classes of progestins. The overall risk varied from a low of 1.895 events/100,000 woman-years for norgestimate OC users to a high of 3.969 events/100,000 woman-years for desogestrel OC users, but these differences were not statistically significant. In the progestin comparison, desogestrel users showed elevated risks for pulmonary emboli and fatalities, norgestrel use was associated with an increased risk of deep vein thrombosis, and norgestimate an increased risk of deep vein thrombosis and pulmonary embolism. Generally, these four groups of low-dose OCs appear safer than any previously published study has indicated. In part, this may reflect PPFA's careful prescribing guidelines. In addition to following US Food and Drug Administration contraindications, PPFA affiliates do not provide OCs to women over 35 years of age who smoke more than 15 cigarettes a day.
JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH. 1998 Dec; 52(12):775-85.The World Health Organization (WHO) Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception has quantified the risks of idiopathic venous thromboembolism (VTE), ischemic and hemorrhagic stroke, and acute myocardial infarction (AMI) associated with use of combined oral contraceptives (OCs). The present case-control study estimated the age-specific incidence and mortality of these four diseases among women with no cardiovascular risk factors and modelled the risks attributable to OC use, smoking, and the interaction of the two. Data sources included relative risk estimates from the WHO study and observed incidence rates obtained from hospitals in UK's Oxford region in 1989-93. The increased risk of VTE associated with OC use among nonsmokers contributed over 90% of all cardiovascular events among women 20-24 years and more than 60% in those 40-44 years. Among OC users who smoked, hemorrhagic stroke and AMI accounted for 80% of cardiovascular deaths in the 20-24 year group and 97% among those 40-44 years. Cardiovascular mortality associated with smoking exceeded that associated with OC use at all ages. Attributable risk associated with OC use was 1 death/year/370,000 users aged 20-24 years, 1/170,000 users aged 30-34 years, and 1/37,000 users aged 40-44 years. Among smokers, annual cardiovascular mortality attributable to OC use was estimated at about 1/100,000 users among women under 35 years old and 1/10,000 users among those 35 years of age and older. Among healthy women 35 years and older, the additional mortality associated with OC use is 1.4/100,000/year compared with 5.4/100,000 among smokers and 14/100,000 women who both use OCs and smoke. Any potential reduction in AMI or stroke risk associated with third-generation OCs would be a more important consideration in older women, especially smokers. However, the mortality associated with smoking is far greater than that associated with use of all types of OCs at all ages.
CONTRACEPTION. 1998 Mar; 57(3):135-6.The eight articles in this issue of "Contraception" should help restore consumer and provider confidence in the safety of combined oral contraceptives (COCs). The papers were commissioned for a 1997 World Health Organization (WHO) Scientific Group Meeting on Cardiovascular Disease and Steroid Hormone Contraception. The complete report will be published in mid-1998 in the WHO Technical Report Series. Overall, these articles suggest that use of low-estrogen COCs by healthy, nonsmoking women is associated with very small increased absolute risks of venous thromboembolism or ischemic stroke. The risk of myocardial infarction or hemorrhagic stroke, if any, is even lower. Regardless of age, the risk of arterial cardiovascular disease attributable to smoking exceeds that associated with COC use. OC providers must ensure that users are informed about conditions that may increase their risk, however. This can be achieved by taking a family and personal history and checking blood pressure. In developing country settings where blood pressure cannot be monitored, women should not necessarily be denied OCs since the risks associated with COC use are negligible compared with those associated with unwanted pregnancy.
Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. Results of an international, multicenter, case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.
CONTRACEPTION. 1998 May; 57(5):315-24.As part of a World Health Organization Collaborative Study conducted at 21 centers in Africa, Asia, Europe, and Latin America in 1989-93, the risks of cardiovascular disease associated with use of oral and injectable progestogen-only and combined injectable contraceptives were investigated. 3697 cases of cardiovascular disease (59% stroke, 31% venous thromboembolism, and 10% acute myocardial infarction) were available for analysis and age-matched with up to three controls. 53 cases were current users of oral progestogen-only contraception, 37 were using an injectable progestogen-only method, and 13 were using combined injectable contraception. The adjusted odds ratios for all cardiovascular diseases compared with nonusers of any type of steroid hormone contraceptive were 1.4 (95% confidence interval (CI), 0.79-1.63) for current users of oral progestogen-only methods, 1.02 (95% CI, 0.68-1.54) for users of injectable progestogen-only contraceptives, and 0.95 (95% CI, 0.49-1.86) for use of combined injectable contraceptives. No significant changes in risk for stroke, venous thromboembolism, or acute myocardial infarction or these three conditions combined was apparent in association with any of the contraceptive methods. However, a nonsignificant increase in risk of venous thromboembolism was apparent for both types of progestogen-only contraceptives. Among women with a history of hypertension, the odds ratio for stroke rose from 7.2 (95% CI, 6.1-8.5) among nonusers of any type of steroid hormonal contraceptive method to 12.4 (95% CI, 4.1-37.6) among current users of all oral progestogens.
[Geneva, Switzerland], WHO, 1997 Apr 24. 3 p. (Press Release WHO/33)A study conducted by the UNDP/UNFPA/WHO/World Bank Special Program of Research, Development, and Research Training in Human Reproduction confirmed that young women in both developed and developing countries with no predisposing risk factors for cardiovascular disease can use oral contraceptives (OCs) without increasing their risk of acute myocardial infarction. The study was conducted in 21 centers in 12 developing and 7 developed countries and involved 369 women with acute myocardial infarction and 941 healthy controls. The duration of OC use did not affect the risk of heart attack. In OC users under 35 years who smoke and use the pill, the incidence of heart attack increases from the 3.5 cases/million woman-years recorded in nonsmoking OC users to about 40 cases/million woman-years. The risk of heart attack rises substantially, however, in OC users over 35 years of age who smoke: to 500 cases/million woman-years. The overall risk of heart attack is 10 times higher in OC users with high blood pressure than in women with normal blood pressure or non-users of OCs. The data did not reveal consistent differences in heart attack risk according to the OC's estrogen dose; there were too few OC users enrolled in the study who were using pills containing gestodene or desogestrel to permit conclusions about the relative safety of second- and third-generation OCs. These findings indicate that the minimal heart attack risk associated with OC use can be avoided by screening women for potential risk factors for such disease, especially high blood pressure, diabetes, and smoking.
WHO Scientific Group Meeting on Cardiovascular Disease and Steroid Hormone Contraceptives. Reunion du Groupe scientifique OMS sur les maladies cardio-vasculaires et les contraceptifs hormonaux steroidiens.
WEEKLY EPIDEMIOLOGICAL RECORD. 1997 Nov 28; 72(48):361-3.More than 100 million women worldwide are thought to use steroid hormone contraceptive methods, with an estimated 93 million women using combined oral contraceptives (COCs). The composition and use of these contraceptive preparations, especially those of COCs, have changed dramatically over the years. The World Health Organization (WHO) convened a Scientific Group Meeting on Cardiovascular Disease and Steroid Hormone Contraception during November 3-7, 1997, to review current scientific data on the use of steroid hormone contraception as they relate to the risk of myocardial infarction, ischemic and hemorrhagic stroke, and venous thromboembolic disease. The group also reviewed the incidence of cardiovascular disease among women of reproductive age in general, how the effect of risk factors for cardiovascular disease may be changed using hormonal contraceptives, and whether different compositions of COCs have different cardiovascular risk profiles. The group was comprised of the authors of background papers prepared for the meeting and experts from around the world. The scientific group's conclusions are presented. The incidence and mortality rates of all cardiovascular diseases are very low among reproductive-age women. For women who do not smoke, who have their blood pressure checked, and who do not have hypertension or diabetes, the risk of myocardial infarction in COC users is not increased regardless of age. While current users of COCs have a low absolute risk of venous thromboembolism, their risk is still 3-6 times greater than that of nonusers, with the risk probably being highest during the first year of use.
Lancet. 1997 Nov 29; 350(9091):1566-7.Available studies on the association between the use of combined oral contraceptives (OCs) and the risk of three serious side effects (myocardial infarction, ischemic and hemorrhagic stroke, and venous thromboembolism) were reviewed at a World Health Organization (WHO) scientific group meeting held in November 1997. The group's findings have been published in the November 28, 1997, issue of "WHO Weekly Epidemiological Record." Of concern to the author of this letter to the editor was the exclusion, with no clear criteria, of many lead investigators from closed sessions. Also notable was the tendency of the panel to downplay controversies about the differences between second- and third-generation OCs in the risk of venous thromboembolism. Moreover, the conclusions on myocardial infarction minimize the likely protective effect of third-generation compared with second-generation OCs. Finally, the summary report does not mention possible bias sources or clarify the lack of clinical and public health significance of odds ratios of 2.0 or less for adverse effects that are extremely rare. In the author's opinion, WHO should have given greater emphasis to the continually improving safety of OCs.