- Email: [email protected]
SMOKING HABITS OF ORAL CONTRACEPTIVE USERS
1228
defect rather than a secondary adaptation of the heart the abnormal haemodynamic situation caused by the communication between the left and right ventricles. De Vries and Saunders,27 on the other hand, whose studies on the differing effects of spiral and lateralised flow on luminal surfaces have demonstrated the interdependence of ontogenetic segmental growth potential
Preliminary Communication
to
and fluid mechanics, confirm that haemodynamic forces not only modify the developing human heart but may do so from a very early age. It therefore seems likely that both factors play a part and that the process has already started at birth, passing unnoticed in the overall picture of ventricular septal defect because minor degrees of obstruction to right ventricular outflow are virtually undetectable by present methods of intracardiac investigation.288 All degrees of narrowing may develop at various sites in the outflow tract, from those that are functionally insignificant to those that divide the right ventricle into two chambers 29,30; and even progression to permanent closure of the pathway connecting the proximal and distal cavities has been reported.31 Walmsley,32 describing the cavity of the normal right ventricle, noted that its two parts could readily be distinguished and that, in the systolic heart, the opening between them " bounded above the crista supraventricularis, below by the moderator band, and at the sides by the extension of these parts on the septum and the anterior wall, is often a small circular foramen "; and the whole question of abnormal muscle bands, hypertrophied muscle bundles, their effects on right ventricular function and consequently upon the natural course of congenital cardiac malformations clearly requires further study. Requests for reprints should be addressed to H. W., Cardiac Department, Royal Infirmary, Dundee DD1 9ND. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
13. 14. 15. 16. 17. 18.
19. 20.
21. 22. 23.
Campbell, M. in Paediatric Cardiology (edited by Hamish Watson); p. 71. London, 1968. Downing, D. F. Am. Heart J. 1959, 57, 669. Wood, P. Br. med. J. 1959, ii, 755. Shah, P., Singh, W. S. A., Rose, V., Keith, J. D. Circulation, 1966, 34, 127. Evans, J. R., Rowe, R. D., Keith, J. D. ibid. 1960, 22, 1044. Bloomfield, D. K. ibid. 1961, 24, 890. Lynfield, J., Gasul, B. M., Arcilla, R., Luan, L. L. Am. J. Med. 1961. 30, 357. Hoffman, J. I. E. Circulation, 1968, 37, 97. Bloomfield, D. K. ibid. 1964, 29, 914. Arcilla, R. A., Agustsson, M. H., Bicoff, J. P., Lynfield, J., Weinberg, M., Jr., Fell, E. H., Gasul, B. M. ibid. 1963, 28, 560. Ash, R. J. Pediatrics, Springfield, 1964, 64, 45. Keith, J. D., Rowe, R. D., Vlad, P. in Heart Disease in Infancy and Childhood; p. 71. New York, 1967. Moore, D., Vlad, P., Lambert, E. C. J. Pediatrics, Springfield, 1965, 66, 712. Nadas, A. S., Scott, L. P., Hauck, A. J., Rudolph, A. M. New Engl. J. Med. 1961, 264, 309. Kaplan, S., Daoud, G. I., Benzing, G., III, Devine, F. J., Glass, I. H., McGuire, J. Am. J. Dis. Child. 1963, 105, 581. Wade, G., Wright, J. P. Lancet, 1963, i, 737. Hoffman, J. I. E., Rudolph, A. M. Am. J. Cardiol. 1965, 16, 634. Taussig, H. B. in Henry Ford Hospital International Symposium on Cardiovascular Surgery (edited by C. R. Lam); p. 119. Philadelphia, 1955. Gasul, B. M., Dillon, R. F., Vrla, V., Hait, G. J. Am. med. Ass. 1957, 164, 847. Muller, W. H., Jr., Dammann, J. F. Jr. Surgery Gynec. Obstet., 1952, 95, 213. Edgett, J. W., Jr., Nelson, W. P., Hall, R. J., Jahnke, E. J., Abby, G. Am. J. Cardiol. 1968, 22, 729. Murthly, K., Arcilla, R. A., Meulder, P. V., Cassels, D. E. J. Am. med. Ass. 1968, 205, 592. Bruins, C. Personal communication.
SMOKING HABITS OF ORAL CONTRACEPTIVE USERS CLIFFORD R. KAY Royal College of General Practitioners’ Oral Contraception
Study ALWYN SMITH Department of Social and Preventive Medicine, University of Manchester BERNARD RICHARDS
Department of Computation, University of Manchester Institute of Science and Technology Summary
Preliminary analyses of data based
on
recruited for observation in a prospective oral-contraception study have revealed that oral-contraceptive users are more likely to be smokers, and to smoke heavily, than non-users. The user and control samples are thought to be representative of their respective populations in the United Kingdom at the present fime. The possible reasons for the difference in smoking habits are immaterial to the conclusion that it might contribute to any observed difference in morbidity or mortality between users and
32,000
women
non-users.
INTRODUCTION
controlled investigations of the morbidity experience of users of oral contraceptives, other possible differences between users and non-users must be taken into account. Users will almost certainly differ from non-users in pregnancy status, marital status, and sexual activity, and probably there will be differences in reproductive history, age, social class, educational background, and personality; and there may be many others. Many differences can be eliminated by matching. However, in the Royal College of General Practitioners’ Oral Contraception Study we are matching only to a limited degree and recording relevant data so that any differences can be assessed during the analysis. We report here a preliminary finding which may have an important bearing on the interpretation of morbidity experience of users of oral contraceptives. IN
METHOD
Approximately general practitioners throughout the United Kingdom are contributing information on an eventual total of 24,000 oral-contraceptive users (takers) and a similar number of non-users (controls). Each doctor is asked to recruit, by a specified random method, 2 takers 1400
24. 25. 26. 27. 28. 29.
30. 31. 32.
R. C. Br. Heart J. 1961, 23, 337. Watson, H., Lowe, K. G. ibid. 1965, 27, 408. Grant, R. P., Downey, F. M., MacMahon, H. Circulation, 1961, 24, 223. De Vries, P. D., Saunders, J. B. de C. M. Contr. Embryol. 1962, 37, 87, no. 256. Watson, H. in Paediatric Cardiology; p. 510. London, 1968. Hartman, A. F., Jr., Tsifutis, A. A., Arvidsson, H., Goldring, D., Circulation, 1962, 26, 279. Lucas, R. V., Jr., Varco, R. L., Lillehei, C. W., Adams, P., Jr., Anderson, R. C., Edwards, J. E. ibid. 25, 443. Perloff, J. K., Ronan, J. A. Jr., de Leon, A. C. Am. J. Cardiol. 1965, 16, 894. Walmsley, T. in Quain’s Elements of Anatomy, E. Sharpey-Schafer, J. Symington and T. H. Bryce; vol. IV, part 3, p. 53. London, 1929.
Brock,
1229 every calendar month. For each taker an age-matched, randomly selected control patient is also recruited from the
practice, and both takers and controls must be married living as married. No other matching is being attempted. Recruitment started on May 1, 1968, and ended on July 31,
same or
the recruited patients will continue the earliest. All records are forwarded to a coordinating office in Manchester where they are processed for computer input, storage, and analysis. At the time of recruitment each patient is interviewed by her general practitioner who records a number of social and medical factors about her. 1969. Observation
until April, 1973,
on
at
RESULT
Besides a number of expected differences between takers and controls in relation to parity and social class, we have encountered a potentially important difference in cigarette consumption at the time of recruitment:
There is a highly significant deficiency of nonsmokers and an excess of heavy smokers in the taker
(X2= 189, P< 0-001). The mean daily cigarette consumption is 6.18 for takers and 5-09 for controls (ratio 1-21/1). We have examined smoking habits in relation to age, parity, and social class. In every category for each subgroup the mean daily cigarette consumption is significantly higher for takers than for controls, except for social class v where consumption is higher (but not significantly) in the controls.
group
DISCUSSION
Controls have been recruited later than their corresponding takers, so that until the recruitment phase is completed there will be an unavoidable deficiency of controls (see table). However, in view of the consistent difference in smoking habits between takers and controls throughout the age, parity, and social-class groups, inclusion of the " missing " controls would be unlikely to affect the result materially. A more serious consideration is that our samples may be unrepresentative. Since there are no suitable published data, either on cigarette smoking or contraceptive usage, we cannot refute this objection, although we are satisfied that our sampling methods are free from obvious sources of error. The participating general practitioners are volunteers who have an interest in research, and their practice populations may in some way reflect this special interest. Nevertheless, the takers and their controls come from the same practices and it is unlikely that these doctors could selectively attract as patients women who both take the pill and have an above-average cigarette consumption, or conversely, women who both smoke little and reject the pill as a method of contraception. It is even less likely that both contingencies could occur simultaneously. We, therefore, believe that the observed relationship between smoking habits and oral contraceptive usage is representative of the population of the United Kingdom at the present time. The same may not be true of other countries and cultures.
We are not here concerned with the sources of the difference in smoking habits: the important factor is the existence of a difference that may influence the morbidity experience of the two groups. We cannot estimate the likely magnitude of this influence since little is known about smoking and morbidity in women of reproductive age. In the United Stateswomen aged 17-44 are reported to have a 40% greater number of days of " restricted activity " due to illness than non-smokers, but the nature of the excess morbidity and the number of episodes of illness are not given. The same publication cites evidence that in-vitro thrombus formation and platelet adhesiveness is increased in smokers, but Vessey and Doll,2 in their extended study, were unable to confirm the suspicion aroused by their earlier observations3 that oralcontraceptive users were more likely to be smokers than were non-users and that smoking could potentiate the liability of the oral contraceptives to cause venous thromboembolic disease. However, Frederiksen and Ravenholt 4,5 believe that Vessey and Doll’s data can be shown to demonstrate such a relationship. We expect that the effect of smoking on the health of young adult women will be among the results of the present study. In the meantime, it is clear that no observed morbid change can be unreservedly attributed to the use of oral contraceptives if the possible influence of associated smoking habits has not been excluded. We appreciate the collaboration of the 1400 general practitioners whose observations are providing the data for this study. The study is supported by a grant from the Medical Research Council. The costs of the pilot trials and current supplementary expenditure have been met by the research foundation board of the Royal College of General Practitioners. The board gratefully acknowledges the receipt of funds for research into oral contraception from Organon Laboratories Ltd., G. D. Searle & Co. Ltd., Schering Chemicals Limited, and Syntex Pharmaceuticals Ltd. Requests for reprints should be addressed to C. R. K., 100 Wilmslow Road, Manchester M14 7DL. REFERENCES
Consequences of Smoking: a Public Health Service Review. Washington, D.C., 1967. Vessey, M. P., Doll, R. Br. med. J. 1969, ii, 651. Vessey, M. P., Doll, R. ibid. 1968, ii, 199. Frederiksen, H., Ravenholt, R. T. ibid. p. 770. Frederiksen, H., Ravenholt, R. T.; Bush, R. D. ibid. 1969, iii, 529.
1. The Health 2. 3. 4. 5.
Hypothesis RELATED DISEASE—RELATED CAUSE? DENIS P. BURKITT External
Staff, Medical Research Council
A constant relationship between certain diseases in different geographical areas or in different socio-economic groups suggests some related ætiological factor. Benign and malignant lesions of the large bowel which show such a relationship are examined, and it is suggested that there is epidemiological and other evidence to incriminate low-residue diet as a major ætiological factor. Summary
INTRODUCTION
STUDIES in disease distribution, both geographically in space and chronologically in time, have not been accorded the emphasis they deserve. It is being in-
defect rather than a secondary adaptation of the heart the abnormal haemodynamic situation caused by the communication between the left and right ventricles. De Vries and Saunders,27 on the other hand, whose studies on the differing effects of spiral and lateralised flow on luminal surfaces have demonstrated the interdependence of ontogenetic segmental growth potential
Preliminary Communication
to
and fluid mechanics, confirm that haemodynamic forces not only modify the developing human heart but may do so from a very early age. It therefore seems likely that both factors play a part and that the process has already started at birth, passing unnoticed in the overall picture of ventricular septal defect because minor degrees of obstruction to right ventricular outflow are virtually undetectable by present methods of intracardiac investigation.288 All degrees of narrowing may develop at various sites in the outflow tract, from those that are functionally insignificant to those that divide the right ventricle into two chambers 29,30; and even progression to permanent closure of the pathway connecting the proximal and distal cavities has been reported.31 Walmsley,32 describing the cavity of the normal right ventricle, noted that its two parts could readily be distinguished and that, in the systolic heart, the opening between them " bounded above the crista supraventricularis, below by the moderator band, and at the sides by the extension of these parts on the septum and the anterior wall, is often a small circular foramen "; and the whole question of abnormal muscle bands, hypertrophied muscle bundles, their effects on right ventricular function and consequently upon the natural course of congenital cardiac malformations clearly requires further study. Requests for reprints should be addressed to H. W., Cardiac Department, Royal Infirmary, Dundee DD1 9ND. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
13. 14. 15. 16. 17. 18.
19. 20.
21. 22. 23.
Campbell, M. in Paediatric Cardiology (edited by Hamish Watson); p. 71. London, 1968. Downing, D. F. Am. Heart J. 1959, 57, 669. Wood, P. Br. med. J. 1959, ii, 755. Shah, P., Singh, W. S. A., Rose, V., Keith, J. D. Circulation, 1966, 34, 127. Evans, J. R., Rowe, R. D., Keith, J. D. ibid. 1960, 22, 1044. Bloomfield, D. K. ibid. 1961, 24, 890. Lynfield, J., Gasul, B. M., Arcilla, R., Luan, L. L. Am. J. Med. 1961. 30, 357. Hoffman, J. I. E. Circulation, 1968, 37, 97. Bloomfield, D. K. ibid. 1964, 29, 914. Arcilla, R. A., Agustsson, M. H., Bicoff, J. P., Lynfield, J., Weinberg, M., Jr., Fell, E. H., Gasul, B. M. ibid. 1963, 28, 560. Ash, R. J. Pediatrics, Springfield, 1964, 64, 45. Keith, J. D., Rowe, R. D., Vlad, P. in Heart Disease in Infancy and Childhood; p. 71. New York, 1967. Moore, D., Vlad, P., Lambert, E. C. J. Pediatrics, Springfield, 1965, 66, 712. Nadas, A. S., Scott, L. P., Hauck, A. J., Rudolph, A. M. New Engl. J. Med. 1961, 264, 309. Kaplan, S., Daoud, G. I., Benzing, G., III, Devine, F. J., Glass, I. H., McGuire, J. Am. J. Dis. Child. 1963, 105, 581. Wade, G., Wright, J. P. Lancet, 1963, i, 737. Hoffman, J. I. E., Rudolph, A. M. Am. J. Cardiol. 1965, 16, 634. Taussig, H. B. in Henry Ford Hospital International Symposium on Cardiovascular Surgery (edited by C. R. Lam); p. 119. Philadelphia, 1955. Gasul, B. M., Dillon, R. F., Vrla, V., Hait, G. J. Am. med. Ass. 1957, 164, 847. Muller, W. H., Jr., Dammann, J. F. Jr. Surgery Gynec. Obstet., 1952, 95, 213. Edgett, J. W., Jr., Nelson, W. P., Hall, R. J., Jahnke, E. J., Abby, G. Am. J. Cardiol. 1968, 22, 729. Murthly, K., Arcilla, R. A., Meulder, P. V., Cassels, D. E. J. Am. med. Ass. 1968, 205, 592. Bruins, C. Personal communication.
SMOKING HABITS OF ORAL CONTRACEPTIVE USERS CLIFFORD R. KAY Royal College of General Practitioners’ Oral Contraception
Study ALWYN SMITH Department of Social and Preventive Medicine, University of Manchester BERNARD RICHARDS
Department of Computation, University of Manchester Institute of Science and Technology Summary
Preliminary analyses of data based
on
recruited for observation in a prospective oral-contraception study have revealed that oral-contraceptive users are more likely to be smokers, and to smoke heavily, than non-users. The user and control samples are thought to be representative of their respective populations in the United Kingdom at the present fime. The possible reasons for the difference in smoking habits are immaterial to the conclusion that it might contribute to any observed difference in morbidity or mortality between users and
32,000
women
non-users.
INTRODUCTION
controlled investigations of the morbidity experience of users of oral contraceptives, other possible differences between users and non-users must be taken into account. Users will almost certainly differ from non-users in pregnancy status, marital status, and sexual activity, and probably there will be differences in reproductive history, age, social class, educational background, and personality; and there may be many others. Many differences can be eliminated by matching. However, in the Royal College of General Practitioners’ Oral Contraception Study we are matching only to a limited degree and recording relevant data so that any differences can be assessed during the analysis. We report here a preliminary finding which may have an important bearing on the interpretation of morbidity experience of users of oral contraceptives. IN
METHOD
Approximately general practitioners throughout the United Kingdom are contributing information on an eventual total of 24,000 oral-contraceptive users (takers) and a similar number of non-users (controls). Each doctor is asked to recruit, by a specified random method, 2 takers 1400
24. 25. 26. 27. 28. 29.
30. 31. 32.
R. C. Br. Heart J. 1961, 23, 337. Watson, H., Lowe, K. G. ibid. 1965, 27, 408. Grant, R. P., Downey, F. M., MacMahon, H. Circulation, 1961, 24, 223. De Vries, P. D., Saunders, J. B. de C. M. Contr. Embryol. 1962, 37, 87, no. 256. Watson, H. in Paediatric Cardiology; p. 510. London, 1968. Hartman, A. F., Jr., Tsifutis, A. A., Arvidsson, H., Goldring, D., Circulation, 1962, 26, 279. Lucas, R. V., Jr., Varco, R. L., Lillehei, C. W., Adams, P., Jr., Anderson, R. C., Edwards, J. E. ibid. 25, 443. Perloff, J. K., Ronan, J. A. Jr., de Leon, A. C. Am. J. Cardiol. 1965, 16, 894. Walmsley, T. in Quain’s Elements of Anatomy, E. Sharpey-Schafer, J. Symington and T. H. Bryce; vol. IV, part 3, p. 53. London, 1929.
Brock,
1229 every calendar month. For each taker an age-matched, randomly selected control patient is also recruited from the
practice, and both takers and controls must be married living as married. No other matching is being attempted. Recruitment started on May 1, 1968, and ended on July 31,
same or
the recruited patients will continue the earliest. All records are forwarded to a coordinating office in Manchester where they are processed for computer input, storage, and analysis. At the time of recruitment each patient is interviewed by her general practitioner who records a number of social and medical factors about her. 1969. Observation
until April, 1973,
on
at
RESULT
Besides a number of expected differences between takers and controls in relation to parity and social class, we have encountered a potentially important difference in cigarette consumption at the time of recruitment:
There is a highly significant deficiency of nonsmokers and an excess of heavy smokers in the taker
(X2= 189, P< 0-001). The mean daily cigarette consumption is 6.18 for takers and 5-09 for controls (ratio 1-21/1). We have examined smoking habits in relation to age, parity, and social class. In every category for each subgroup the mean daily cigarette consumption is significantly higher for takers than for controls, except for social class v where consumption is higher (but not significantly) in the controls.
group
DISCUSSION
Controls have been recruited later than their corresponding takers, so that until the recruitment phase is completed there will be an unavoidable deficiency of controls (see table). However, in view of the consistent difference in smoking habits between takers and controls throughout the age, parity, and social-class groups, inclusion of the " missing " controls would be unlikely to affect the result materially. A more serious consideration is that our samples may be unrepresentative. Since there are no suitable published data, either on cigarette smoking or contraceptive usage, we cannot refute this objection, although we are satisfied that our sampling methods are free from obvious sources of error. The participating general practitioners are volunteers who have an interest in research, and their practice populations may in some way reflect this special interest. Nevertheless, the takers and their controls come from the same practices and it is unlikely that these doctors could selectively attract as patients women who both take the pill and have an above-average cigarette consumption, or conversely, women who both smoke little and reject the pill as a method of contraception. It is even less likely that both contingencies could occur simultaneously. We, therefore, believe that the observed relationship between smoking habits and oral contraceptive usage is representative of the population of the United Kingdom at the present time. The same may not be true of other countries and cultures.
We are not here concerned with the sources of the difference in smoking habits: the important factor is the existence of a difference that may influence the morbidity experience of the two groups. We cannot estimate the likely magnitude of this influence since little is known about smoking and morbidity in women of reproductive age. In the United Stateswomen aged 17-44 are reported to have a 40% greater number of days of " restricted activity " due to illness than non-smokers, but the nature of the excess morbidity and the number of episodes of illness are not given. The same publication cites evidence that in-vitro thrombus formation and platelet adhesiveness is increased in smokers, but Vessey and Doll,2 in their extended study, were unable to confirm the suspicion aroused by their earlier observations3 that oralcontraceptive users were more likely to be smokers than were non-users and that smoking could potentiate the liability of the oral contraceptives to cause venous thromboembolic disease. However, Frederiksen and Ravenholt 4,5 believe that Vessey and Doll’s data can be shown to demonstrate such a relationship. We expect that the effect of smoking on the health of young adult women will be among the results of the present study. In the meantime, it is clear that no observed morbid change can be unreservedly attributed to the use of oral contraceptives if the possible influence of associated smoking habits has not been excluded. We appreciate the collaboration of the 1400 general practitioners whose observations are providing the data for this study. The study is supported by a grant from the Medical Research Council. The costs of the pilot trials and current supplementary expenditure have been met by the research foundation board of the Royal College of General Practitioners. The board gratefully acknowledges the receipt of funds for research into oral contraception from Organon Laboratories Ltd., G. D. Searle & Co. Ltd., Schering Chemicals Limited, and Syntex Pharmaceuticals Ltd. Requests for reprints should be addressed to C. R. K., 100 Wilmslow Road, Manchester M14 7DL. REFERENCES
Consequences of Smoking: a Public Health Service Review. Washington, D.C., 1967. Vessey, M. P., Doll, R. Br. med. J. 1969, ii, 651. Vessey, M. P., Doll, R. ibid. 1968, ii, 199. Frederiksen, H., Ravenholt, R. T. ibid. p. 770. Frederiksen, H., Ravenholt, R. T.; Bush, R. D. ibid. 1969, iii, 529.
1. The Health 2. 3. 4. 5.
Hypothesis RELATED DISEASE—RELATED CAUSE? DENIS P. BURKITT External
Staff, Medical Research Council
A constant relationship between certain diseases in different geographical areas or in different socio-economic groups suggests some related ætiological factor. Benign and malignant lesions of the large bowel which show such a relationship are examined, and it is suggested that there is epidemiological and other evidence to incriminate low-residue diet as a major ætiological factor. Summary
INTRODUCTION
STUDIES in disease distribution, both geographically in space and chronologically in time, have not been accorded the emphasis they deserve. It is being in-