Decline in cerebral thromboembolism among younger women after introduction of low-dose oral contraceptives. A study of the incidence for the period 1980-1995 (original) (raw)
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Contraception, 1995
The aim of this study was to analyze age-specific incidence rates (IRS) of cerebral thromboembolic attacks (CTA) among women and men 1544 years of age in Denmark from 1980 through 1993 and to quantify possible influences from oral contraceptives (OC) on the incidence figures. The discharge diagnoses ICD 432-436 from all Danish neurological, neurosurgical and medical departments during the period 1980-l 993 were identified in a central diagnosis register. The use of OC was achieved from complete sale statistics during the study period and crosssectional studies assessing the type-specific use of OC at different ages. During the 14-year study period, 2,100 female and 2,552 male attacks were registered. Men had an exponentially increasing IR with increasing age. Compared with men in the period 1980-86, women had more attacks in the 20-35year age group and fewer attacks above the age of 35. After 1987 the sex differences below the age of 35 were not significant. From the first half (198tL-86) to the last half (1987)(1988)(1989)(1990)(1991)(1992)(1993) of the study period, women below 30 years had a significantly falling CTA IR of -20.4%, compared with a non-significant fall of -9.5% among men below 30 years. In the age group above 30 years, women experienced a not significant increase of 4.2%, men a significant increase of 11.4%. Assuming that use of OC implied an average relative risk of CTA of 2.5 and pregnancy a relative risk of 4, a correction was made for the contribution of incident cases among women. The corrected IRS had a close co-variation with the IRS of men up to the age of 35. Thereafter, men had higher IR as is the case for older age groups. It is concluded that women's pregnancies and use of OC may explain the higher IRS of CTA in young fertile age compared to those of men. The more pronounced fall in IRS among young women compared with young men through the last 14 years may be a consequence of the reduced hormonal content of OC. CONTRACEPTION 1995; 85-92 KEY WORDS: cerebral thrombosis, cerebral embolism, cerebrovascular disease, cerebrovascular disorders, epidemiology, oral contraceptives, Denmark ISSN OOlO-7824/95/$9.50 SSDI OOlO-7824(95)00138-Z
Oral contraception and risk of a cerebral thromboembolic attack: results of a case-control study
BMJ, 1993
Objective-To assess the risk ofcerebral thromboembolism in women using low dose oral contraceptives. Design-A retrospective case-control study. Setting-All Danish medical, neurological, neurosurgical, and gynaecological departments. Subjects-All 794 women in Denmark aged 15-44 who had suffered a cerebral thromboembolic attack during 1985-9 and 1588 age matched randomly selected controls. Results-Of 692/1584 case/control questionnairs sent out, 590/1396 (85.30/./8811/6) were returned. Among the cases, 15 refused to participate, 69 had a revised or unreable diagnosis, 40 had had thromboembolic disease previously, 13 were pregnant, and 152 had a disease predisposing to a cerebral thromboembolic attack. Of the 323 cases only pills did not increase the risk of a cerebral Department ofObstetrics thromboembolic attack.
Cerebral thromboembolism among young women and men in Denmark 1977-1982
Stroke, 1986
In the period 1977-1982, the Danish National Patient Register recorded 1000 cases of cerebral thromboembolic attacks among women 15-44 years of age, and 971 cases among men of the same age. Cerebral infarction accounted for 70% of cases and transient ischemic attacks (TIA) for the remaining 30%. By analysing this material we found an average age-adjusted incidence rate of cerebral thromboembolism of 14.4/100.000 among men and 15.5/100.000 among women. The incidence rates rose rapidly with increasing age. Women aged 15-34 had significantly higher Incidence rates of brain infartlon and TIA compared to those of men of the same age. This was reversed hi the age group 35-44. The magnitude of the ratio between the female and the male mean incidence rates by Increasing age corresponded exactly to the age distribution of the use of oral contraceptives hi Denmark. The relative risk for developing cerebral thromboembolism among users of oral contraceptives was estimated to be 3.2-6.5. The mortality in male patients with brain infarction was 3.3% and hi females 1.7%. The mean duration of stay hi hospital was 8.8 days for TIA and about 26 days for cerebral Infarction. Sixteen percent of men and 13.6% of women had hypertension during then-stay.
Contraceptives and cerebral thrombosis: a five-year national case-control study☆
Contraception, 2002
The object of this study was to assess the influence of oral contraceptives (OCs) on the risk of cerebral thromboembolic attacks (CTA) including thrombotic stroke and transitory cerebral ischemic attacks. A 5-year case-control study including all Danish hospitals was conducted. All women 15-44 years old suffering a first ever CTA during the period January 1, 1994 to December 31, 1998, were included. Controls were selected annually, 600 per year in 1994 -1995, 1200 per year 1996 -1998. Response rates for cases and controls were 88% and 90%, respectively. After exclusion of nonvalid diagnoses, pregnant women, and women with previous thrombotic diseases, 626 cases and 4054 controls were available for analysis.
Cerebrovascular deaths before and after the appearance of oral contraceptives
Acta Neurologica Scandinavica, 1987
The mortality of cerebrovascular diseases in Denmark was analysed for men and women 15-44 years of age, in a 14-year period before and after the appearance of oral contraceptives (OC) in 1966. 1,670 deaths were registered over 28 years, during which the female incidence of cerebrovascular deaths increased by 19% (P<0.025), while the male mortality was unchanged. Women showed a percentage increase in deaths from cerebral thromboembolic attacks (CTA) of 33%, men a fall of 14%. The increase of female CTA deaths was most pronounced in the young fertile group, the age group with a high OC use. A relative risk of CTA of 3.3-4.5 for OC users compared with non-users could explain the CTA trend difference between women and men. No other single risk factor responsible for the observed trends could be identified. Both women and men had a significant increase in the mortality of subarachnoidal hemorrhages, and a significant fall in the mortality of intracere-bra1 hemorrhages.
Thrombotic diseases in young women and the influence of oral contraceptives*1
American Journal of Obstetrics and Gynecology, 1998
In the evaluation of the clinical impact of thrombotic diseases in young women, age-specific incidence rates must be calculated for both arterial and venous thrombotic diseases, but also the case-fatality rate and figures for the clinical consequences among those who survive thrombosis must be included. The aim of this analysis was to quantify the clinical impacts of both arterial and venous thrombotic diseases among young, nonpregnant women and thereafter to assess the influences of oral contraceptives on these measures. STUDY DESIGN: Nationwide register data on the morbidity and mortality of venous thromboembolism, myocardial infarction, and thrombotic stroke in Denmark, 1980-1993, and 3 ongoing case-control studies to assess the influence of oral contraceptives on the risk for development of these thrombotic diseases. RESULTS: In women 15-29 years old venous thromboembolism is about twice as common as arterial complications, whereas in women 30-44 years old the number of arterial complications exceeds that of venous diseases by about 50%. The mortality rate from arterial diseases is 3.5 times higher than that from venous diseases among women <30 years old and 8.5 times higher than that from venous diseases in women 30-44 years old. The proportion of women with a significant disability among women who had an arterial complication was about 30%; the proportion was about 5% among women with venous thromboembolism. CONCLUSION: Anticipating a differential influence on venous and arterial diseases from oral contraceptives with second-and third-generation progestogens, it was calculated that users of oral contraceptives with second-generation progestogens had 30% greater increased risk of thrombotic diseases, 260% greater increased risk of thrombotic deaths, and 220% greater increased risk of thrombotic disability than users of oral contraceptives with third-generation progestogens.
BJOG: An International Journal of Obstetrics and Gynaecology, 1995
Objective To assess the risk of developing cerebral thromboembolism among pregnant women and among fertile women with hypertension, migraine, diabetes, and previous thrombotic disease, and to investigate the interaction of these risk factors with the use of oral contraceptives. Design A retrospective case-control study. Setting All gynaecological, medical, neurological, and neurosurgical departments in Danish hospitals. Subjects Seven hundred and ninety-four women in Denmark aged 15 to 44 who suffered a cerebral thromboembolic attack during the period 1985 to 1989 and 1588 age-matched, randomly selected controls. Response Of the 692 case and 1584 control questionnaires sent out, 590 (85.1 %) and 1396 (88.1 %), respectively, were returned. Of the 590 cases, nine had had cerebral thrombosis before 1980, 15 refused to participate, 44 had a revised diagnosis (primarily multiple sclerosis) and 25 had an unreliable diagnosis, leaving 497 with a reliable cerebral thromboembolic diagnosis. Among the 1396 controls, 26 either refused to participate, were mentally handicapped, lived abroad or returned an uncompleted questionnaire, leaving 1370 controls included in the study. Results After multivariate analysis, pregnancy implied an odds ratio (OR) for a cerebral thromboembolic attack of 1-3 (nonsignificant), diabetes an OR of 5.4 (P < 0.001), hypertension an OR of 3.1 (P < 0.001) and migraine an OR of 2.8 (P < 0.01). Women with previous non-cerebral thrombotic disease had an OR for cerebral thrombo-embolism of 5.3 (P < 0.001). Women with other predisposing medical diseases had an OR of 8.3 (P .c 0.001). These ORs were identical among users and non-users of combined oral contraceptives. Conclusion In this study pregnancy implied a non-significant elevated odds ratio of 1-3 for cerebral thromboembolism whereas diabetes, hypertension, migraine and past thromboembolic events increased the risk of cerebral thromboembolism significantly. Women with these increased thrombotic risks should use oestrogen-containing oral contraceptives only after careful considerations of the risks, if at all. Cerebral thromboembolic attacks (CTA) include occlusion of pre-cerebral arteries (ICD 432), cerebral thrombosis (ICD 433), cerebral embolism (ICD 434), transient cerebral ischaemic attack (ICD 439, and the unspecified group of cerebral apoplexy (ICD 436), of which thrombotic cases have been found to constitute 80 to 90 % (Robins & Baum 1981 ; Walker et al. 1981 ; Mettinger et al. 1984a).
2014
The objective of this study was to assess the influence of oral contraceptives (OCs) on the risk of venous thromboembolism (VTE) in young women. A 5-year case-control study including all Danish hospitals was conducted. All women 15–44 years old, suffering a first ever deep venous thrombosis or a first pulmonary embolism (PE) during the period January 1, 1994, to December 30, 1998, were included. Controls were selected annually, 600 per year in 1994–1995 and 1200 per year 1996–1998. Response rates for cases and controls were 87.2 % and 89.7%, respectively. After exclusion of nonvalid diagnoses, pregnant women, and women with previous thrombotic disease, 987 cases and 4054 controls were available for analysis. A multivariate, matched analysis was performed. Controls were matched to cases within 1-year age bands. Adjustment was made for confounding influence (if any) from the following variables: age, year, body mass index, length of OC use, family history of VTE, cerebral thrombosis o...