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New epidemiological studies have demonstrated a higher risk of venous thromboembolism among users of oral contraceptives (OCs) with third-generation progestogens desogestrel or gestodene compared with users of OCs with second-generation progestogens levonorgestrel or norgestrel. As the absolute risk of venous thromboembolism among users of OCs in general is lower in the new studies than in previously published studies, and as several important potential confounders are not controlled for in the new studies, the real difference in risk of venous thromboembolism between users of third- compared with second-generation products may be smaller than indicated in these new studies. At the same time, the risk of myocardial infarction may be smaller among users of third- compared with users of second-generation products. Until further epidemiological data emerge, it is therefore difficult to make general recommendations other than to use OCs with a low estrogen dose, and to make individual recommendations based on age, individual wish, and individual risk factors.

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 less than 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 intracerebral hemorrhages.The aim of this study was to investigate cerebrovascular deaths in Denmark in 15-44 year old men and women for the 14-year period prior to the introduction of oral contraceptives (OCs) in late 1966 compared with the subsequent 14 years. Study data were derived from annual vital statistics from 1953-80. A total of 1670 cerebrovascular deaths were recorded over the 28 years reviewed. During this period, the female incidence of cerebrovascular deaths increased by 19% while male mortality was constant. However, there were differences within the 3 subgroups of cerebrovascular deaths. In terms of cerebral thromboembolism, there was a 33% increase among women in the death rate between the 2 periods studied contrasted with a 14% decline in deaths among men. The female rate increase was most marked in the 15-34-year age group. Deaths from subarachnoid hemorrhage increased significantly for both sexes between the 2 periods--38% for men and 67% for women. Here, the increases in mortality were greatest for men and women 35-44 years of age. Finally, deaths from intracerebral hemorrhages fell by 37% for men and 22% for women during the study periods. The etiology of cerebral thromboembolism is multifactorial, involving factors such as diet, hypertensive control, cigarette smoking, and occupational thrombogenic factors. However, the dramatic increase of 33% recorded among women in deaths from cerebral thromboembolism after 1966 seems to suggest that OCs have played a significant role in the changes in female deaths from this cause. Further epidemiological studies are necessary to support or reject the hypothesis that OCs have had a major impact on the mortality profile of young women in recent years.

Ever since 1961, there has been discussion on possible thromboembolic effects from the use of oral contraceptives. The purpose of this Danish study was to determine if birth-control pill users did have an increased risk of venous thromboembolic disease (VTD), including deep venous thrombosis and pulmonary embolism. In previous research, morbidity from VTD has been found to show a great variance, as high as 1/330 woman years in 1 study to as low as 1/5,000 woman years in another. In these studies no significant difference was found between users and non-users of oral contraceptives. Only in 1 study was there found to be increased morbidity from VTD among pill users: 1/5,200 woman years, compared with 1/35,000 woman years for non-pill users. As a possible explanation of the pill's effect, several studies have demonstrated a rise in certain coagulation factors, increased fibrinogen and lowered antithrombin III. In the present study, medical records of all women aged 34 or under who had been referred to a Copenhagen hospital between 1981 and 1983 for treatment of phlebographic-or lungescintographic-confirmed VTD were investigated. After controlling for exclusion factors, there remained 35 test subjects between the ages of 16 and 34 (median age 22). Of the 22 cases of known etiology, 16 suffered from iatrogenic VTD. Of 13 women who suffered from VTD of unknown etiology, 69% were pill users, compared with only 29% (a significant difference) in a background-population interview study conducted in Denmark during 1983. With a known disposition to VTD, oral-contraceptive usage meant a relative risk of 0.9 for developing the disease, which figure conforms well with other cited research (in which the risk factor varied from 0.4 to 3.8).

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 infarction and TIA compared to those of men of the same age. This was reversed in 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 in 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 in females 1.7%. The mean duration of stay in 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 their stay.