Oral contraceptives and thromboembolic disease.
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Biomedical subjects
Publications and source records attributed to R Doll.
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The results of a previous study of the use of oral contraceptives by married women discharged from hospital with a diagnosis of thromboembolic disease in the years 1964-6 were reported by us last year. The present paper adds results relating to patients discharged during 1967 and a few data, that could not be sought previously, for patients discharged with cerebral or coronary thrombosis from three of the hospitals in the earlier period.Of 84 patients with deep-vein thrombosis or pulmonary embolism 42 (50%) had used oral contraceptives during the month preceding the onset of their illness, while only 23 of the 168 controls (14%) had done so. No differences in risk were found either for the types of preparation or for the duration of use. After allowance for age and height, the patients with venous thromboembolism were about 10 lb. (4,535 g.) heavier than the control patients, irrespective of whether they were using oral contraceptives or not. No appreciable difference was found between the smoking habits of patients with and without venous thromboembolism treated during 1967, nor between women who were using oral contraceptives and those who were not. The trend in hospital admissions for venous thromboembolism with time corresponded to the trend in the use of oral contraceptives, and there was no evidence to suggest that the number of admissions was affected by publicity about the risk of using the preparations. Of 19 patients with cerebral thrombosis 11 (58%) had been using oral contraceptives, compared with an expected figure of 3.5 from the experience of the control subjects. All the published data (clinical, angiographic, and post-mortem) show that the thrombosis affects the cerebral arteries rather than the cerebral veins. Of 17 patients with coronary thrombosis 2 (12%) had been using oral contraceptives, compared with an expected figure of 2.1. The patients with coronary thrombosis smoked more than the control patients and were, on average, 8.3 lb. (3,765 g.) heavier than control women of the same age and height.The new evidence strengthens the belief that oral contraceptives are a cause of venous thromboembolism and cerebral thrombosis but does not indicate that they are a cause of coronary thrombosis.
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The mortality attributed to asthma has increased annually in England and Wales from 1960 to 1965. The increase is more pronounced at ages 5 to 34 years than at older ages and is most pronounced at ages 10 to 14 years. In this last age group the mortality increased nearly eight times in seven years, and in 1966 asthma accounted for 7% of all deaths. No comparable increase has been observed in any other country, but smaller increases at ages 10 to 19 years have been observed in Australasia, Japan, western Europe, and the United States. There is no evidence to suggest that there has been any change in diagnostic habits, certification of deaths, or methods of classification which could account for the increase in Great Britain, and it is concluded that the increase is real. General practitioners' records provide no evidence of an increase in prevalence and it seems probable that there has been an increase in case fatality. No environmental hazards are known which could have increased the severity of the disease, and the possibility has to be considered that the increase may be due to new methods of treatment. Corticosteroids have been used increasingly since 1952, and in Great Britain the use of pressurized aerosols containing sympathomimetics has increased rapidly since 1960.
Copies of death certificates were provided by the Registrar General for all deaths attributed to asthma in persons aged 5 to 34 years which were registered in England and Wales in the last quarter of 1966 and the first quarter of 1967. Information was obtained from the relevant general practitioners about 177 of the 184 subjects, and necropsy data were obtained for 113 of the 124 cases in which a post-mortem examination was known to have been made. Ninety-eight per cent. of the subjects for whom evidence was obtained were known to have been suffering from asthma, and signs of severe asthma (overdistended lungs and small bronchi plugged with mucus) were found in 91% of necropsies (57% of all deaths). Evidence that death might have been due to any other pathological condition was rare. Death was sudden and unexpected in 81% of the subjects (137 out of 171), and 59% of all deaths were referred to coroners. In 39% of cases (67 out of 171) the practitioner had not regarded the patient as suffering from severe asthma in his terminal episode. Corticosteroids and sympathomimetic preparations were the only drugs to have been used by a large proportion of patients. Two-thirds of the patients had received corticosteroids before the terminal episode, but detailed information about their use provided no suggestion that excess use could have been responsible for any large proportion of the deaths. Eighty-four per cent. of the patients were known to have used pressurized aerosol bronchodilators, and several instances of their use in excess were described. Routine inquiries about their use in the hours immediately preceding death were not made, and further evidence is required before their effect can be assessed adequately.
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