Thromboembolic Disease and the Steroidal Content of Oral Contraceptives. A Report to the Committee on Safety of DrugsBr Med J 1970; 2 doi: https://doi.org/10.1136/bmj.2.5703.203 (Published 25 April 1970) Cite this as: Br Med J 1970;2:203
- W. H. W. Inman,
- M. P. Vessey,
- Barbro Westerholm,
- A. Engelund
Reports of thromboembolism following the use of oral contraceptives received by drug safety committees in the United Kingdom, Sweden, and Denmark have been analysed to investigate possible differences in the risks associated with the various preparations. For this purpose the numbers of reports of thromboembolism attributed to each product were compared with the distribution that would have been expected from market research estimates of sales, assuming that all products carried the same risk.
A positive correlation was found between the dose of oestrogen and the risk of pulmonary embolism, deep vein thrombosis, cerebral thrombosis, and coronary thrombosis in the United Kingdom. A similar association was found for venous thrombosis and pulmonary embolism in Sweden and Denmark. No significant differences could be detected between sequential and combined preparations containing the same doses of oestrogen, nor between the two oestrogens, ethinyloestradiol and mestranol.
Certain discrepancies in the data suggest that the dose of oestrogen may not be the only factor related to the risk of thromboembolism; thus there was a significant deficit of reports associated with the combination of mestranol 100 μg. with norethynodrel 2·5 mg. and a significant excess of reports associated with the combination of ethinyloestradiol 50 μg. with megestrol acetate 4 mg. An excess of reports also occurred with other combined preparations containing megestrol acetate.
The data obtained in earlier epidemiological studies were re-examined and, though no trend was obvious in any one of them, the combined results showed an excess of cases of thromboembolism at the highest dose of oestrogen.
The finding of a positive correlation between the dose of oestrogen and the risk of coronary thrombosis is of special interest since previous studies have failed to provide clear evidence of a relationship between oral contraceptives and this condition.