V WYNN. I F GODSLAND. J C STEVENSON. Wynn Institute for M\etabolic Research. ... In our view, Professor V Wynn and colleagues ..... WILLIAM KEARNS.
control study.' We were also interested to see that Professor Vessey and colleagues provide further support (albeit based on very small numbers) for our previous finding that past use of the contraceptive pill mav increase a woman's risk of subarachnoid haemorrhage. We are puzzled by the authors' use of analyses that are based on the contraceptive state of the women at entry to the study. There were 5555 women years of current use and presumably about 10000 women years of subsequent observation as former users that have been wrongly included in the data for users of a diaphragm or intrauterine device. Thus the misclassification of any deaths that occurred in these users of the contraceptive pill would tend to underestimate the risk associated with use. In addition, fewer users of the contraceptive pill recruited to the study smoked (36%)h than those entered into the Royal College of General Practitioners study (48%).- Because smoking has an important influence on contraceptive pill users' risk of dying from a circulatory disorder2 we would expect the two studies to produce different overall estimates of risk. We are planning to reanalyse our mortality data, which are based on about 900 deaths. These results will be much more appropriately comparable with those of Professor Vessey and colleagues. PHILIP C HANNAFORD CLIFFORD R KAY
Royal College of General Plractitioners, Manchester Research Unit, Manchester M120 oTrR I Vessev MPl', Villard-Mlackintosh L, M1cPherson K, Yeates D. Mortality amottg oral contraceptive tisers: 20 year follow up of women in a cohort study. Br Med ] 1989;299:1487-91. 16
December.) 2 Royal College ofGencral l'ractitioners' Oral Contraception Stuldy Group. Further analyses of mortality in oral contraceptiVe users. Lancet 1981;i:541-6. 3 Vessev Ml'. Female hormones and vascular disease-an epidcmiological overview. British Joumnal oJf Family, Plannittg 1980;6(suppl): 1-12. 4 Slone D, Shapiro D, Kaufman DW, Rosenberg L, Miettinen OS, Stolley PD. Risk of myocardial infarction in relation to current and discontinued use of oral contraceptives. N Engl J Med
women who had stopped using the contraceptive pill six or more years before death. Despite these findings Professor Vessey and colleagues surprisingly state that their results "give no cause for concern" as in the cohort as a whole increased risk of ischaemic heart disease is countered by a reduced risk of some cancers. We do not think that this statement is justifiedindividual women who develop ischaemic disease while taking the contraceptive pill will hardly be reassured by the fact that they have a reduced risk of cancer. The authors draw further encouragement from the relative risk of 1 5 for all cardiovascular disease in their oral contraceptive users compared with a risk of 4-2 reported by the Royal College of General Practitioners in 1981.2 The figure reported by Professor Vessey and colleagues relies substantially on the fact that "other circulatory diseases," ofwhich the relevant International Classification of Diseases codes list 42, caused only three deaths in women who were using oral contraceptives as opposed to six in women who were using a diaphragm. If we consider those with ischaemic heart disease and cerebrovascular disease-conditions in which use of oral contraceptives is known to increase mortality-then there were 22 deaths in the users of oral contraceptives but only six in the non-users. This suggests a substantial increase in risk. Furthermore, the analysis deals only with deaths. Non-fatal ischaemic heart disease and stroke are more common than fatal forms of both in women in this age group, and this aspect needs to be examined in detail. It would be unfortunate if the lack of a difference in overall mortality between oral contraceptive users and non-users in the Oxford-Family Planning Association study was allowed to obscure the fact that there is still work to be done in improving the risk to benefit ratio, particularly with respect to cardiovascular disease. On the basis of the authors' analysis modification of oral contraceptive formulation to this end could offer the possibility of an eventual net benefit of oral contraceptive use. V WYNN I F GODSLAND J C STEVENSON
1981;305:420-4. 5 Rosenberg L, Palmcr JR, Shapiro S. Oral contraceptive use and myocardial iniarction. 3m] Ipidemiol 1988;128:921-2. 6 Vessey MI, Dosll R, 1'eto R, Johnson B, Wiggins P. A long-term follow-up study otf wotnen using different methods of contraception -an interim report. ] Biosoc Sci 1976;8:373-427. 7 Royal College of General P'ractitioners. Oral contraceptinves ad health. London: PitmanAMedical, 1974. 8 Roval College of General P'ractitioners Oral Contraccptioni Study Group. Ittcidence of arterial discase among oral contraceptive users. _7 R Coll GensIract 1983;33:75-82.
Wynn Institute for M\etabolic Research. London NWY, 9SQ I Vessev Mil', Villard-Mackintosh L, McPherson K, Yeates D. Mortalitv among oral contraceptive users: 20 vear follow up of women in a cohort study. Br Aled J 1989;299:1487-91.
(16 December ) 2 Royal College of General Practitioners Oral Contraccption Study Group. Fttrther analyses of mortality in oral ctontraceptive users. Lancet
SIR,-In the study of mortality among users and non-users of oral contraceptives by Professor M P Vessey and colleagues the outcome measures were mortality due to various neoplasms, diseases of the circulatory system, accident and violence, and other causes. The study was handicapped by an inadequate number of events that was associated with the relatively low mortality in the cohortabout half of that which would have been expected judged by age specific mortality figures for women in England and Wales for 1980, a representative year for the women at risk. The authors acknowledge these difficulties and draw attention to the lack of power of the study for detecting even major defects after subdivision of the data for individual diseases. Despite these difficulties the study produced some remarkable findings. For example, of the eight women who died of cancer of the cervix, seven were oral contraceptive users. However, none of the findings were significant. The results of most interest to us relate to diseases of the circulatory system. Ischaemic heart disease as a cause of death was 3 3 times more common in women who used or had used oral contraceptives compared with non-users. This finding agrees with other published data. An important observation was that the excess mortality from ischaemic heart disease was also apparent in
BMJ
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1981;i:541-6.
AUTHORS' REPLY,-The differences that Drs Philip C Hannaford and Clifford R Kay point out between our study and that of the Royal College of General Practitioners might go some way towards explaining the discrepant findings with respect to cardiovascular mortality. While it is true that we based our main analysis on the experience of the entry cohorts, we also provided information on deaths from ischaemic heart disease and subarachnoid haemorrhage by total duration of oral contraceptive use and by recency of use. The overall results obtained in these analyses were essentially the same as those found in the main analysis. In our view, Professor V Wynn and colleagues have lost sight of the main objective of our analysis-that is, to provide an overall view of risks and benefits of oral contraceptive use. This analysis indicated that the overall relative risk of death in oral contraceptive users was 0-9 (95% confidence interval 0 7 to 1 2) compared with users of a diaphragm or intrauterine device. In our report we focus on the relative risk of death for all cardiovascular diseases of 1-5 in users of the contraceptive pill as opposed to the corresponding relative risk of 4 2 in the Royal College of General
Practitioners study because the royal college's figure has been extensively quoted in the scientific and lay press. If we concentrate only on ischaemic heart disease and stroke the numbers of deaths in those using the contraceptive pill at entry and those using a diaphragm or intrauterine device at entry are indeed 22 and six respectively, but the corresponding rates per 100 000 woman years are 13 4 and 5 7. This is because the denominators are not equal in the groups being contrasted and because of the influence of confounding factors. Finally, we have already analysed data on non-fatal cardiovascular disease in the Oxford-Family Planning Association study. Two of the references are given in our report, while the third is given below. MARTIN VESSEY LAURENCE VILLARD-MACKINTOSH KLIM McPHERSON DAVID YEATES Department of Community Medicine and General P'ractice, Radcliffe Infirmarn, Oxford OX2 6HE I Mant D, Villard-Mackintosh L, Vessey MP, Yeates D. Mvocardial infarction and angina pectoris in young women. 7 Epidemi'ol Community, Health 1987;41:215-9.
SIR,-The results of the Oxford-Family Planning Association cohort study published over the years by Professor M P Vessey have provided invaluable information about oral contraceptives and other methods. This has helped in providing birth control methods that combine the maximum efficiency with the minimum risk for each individual. The latest report' is encouraging as it shows a mortality from circulatory diseases (relative risk 1 5) that is substantially less than that found in the Royal College of General Practitioners study (relative risk 4 2).2 Of the 18 deaths due to ischaemic heart disease that occurred in the Oxford study, only one was in a woman who did not smoke and 15 were in women with other relevant risk factors. Only two of the 28 women who died from ischaemic heart disease and cerebrovascular disease were taking the
