Commentary: Tobacco-related diseases: a gender differential?

Eva Prescott

Institute of Preventive Medicine, Kommunehospitalet, DK 1399 Copenhagen, Denmark. E-mail: eva.prescott{at}dadlnet.dk

Several of the earlier studies on smoking-related mortality have shown lower risks in female compared to male smokers due to limited smoking exposure in the generations of smokers that these studies were based on. Studies that include many heavily smoking women such as the Renfrew and Paisley Study are therefore welcome. A previous study based on a sample of the population in Copenhagen, Denmark, which also has a high prevalence of smoking among women, suggested gender differences in effects of smoking on cause-specific and all-cause mortality. These findings could not be reproduced using data from the Renfrew and Paisley study in Scotland1 and possible explanations are warranted.

The two study populations seem very similar: they were both representative of the general population, they were sampled in the 1970s, they included a large number of men and women of similar age groups and smoking rates were high. In fact, Denmark and Scotland are very similar in that in both countries women took up smoking early in the smoking epidemic and the prevalence of smoking among women is now among the highest in the world.2

In the Danish study population we have found gender differences in smoking-related risk of cardiovascular disease3 and chronic obstructive pulmonary disease (COPD),4 but not in lung cancer.5 For COPD similar results have been shown in several studies68 although only few studies have used hard end-points and none have used mortality data. Respiratory diseases account for only approx 6% of all deaths and a study of gender difference in smoking-related mortality risk would need very large population samples. However, according to the Danish mortality statistics, mortality rates from COPD in the age group 45–54 years have been higher in women than in men since 1985, and since 1990 this has also been the case for the age group 55–64 years (personal communication, K Juel, National Institute of Public Health). This is surprising since these generations of women have accumulated smoking exposures that are considerably lower than the men's. This may in part be due to competing risks, but the higher mortality rates in women may also indicate difference in susceptibility since COPD is almost solely caused by smoking.

For cardiovascular disease, earlier studies such as the British Doctors study and the Framingham study have found smaller relative risks (RR) in women.9,10 However, several more recent studies find higher RR in women11,12 and an interesting hypothesis is that in women the anti-oestrogenic effect of smoking should be added to the thrombogenic effect. Naturally, cardiovascular disease is multifactorial and other strong risk factors may vary differently according to smoking status in women and men, and in different study populations. An attempt to adjust for this was done in the Danish study population which still yielded significantly higher RR associated with smoking in women than in men after adjustment.3 Interestingly, a similar results were found in the Scottish Heart Health Study.13

Thus in the Danish study sample these gender differences seem relatively stable. Marang-van de Mheen and co-authors suggest the differences between the two findings may be due to the fact that in the Danish study non-cigarette smokers were included. We have not had the opportunity to repeat our analyses on the entire data-set but in the Copenhagen City Heart study, which constituted approximately half of the data in our original study, 19% if the women and 43% of the men were non-cigarette smokers. Taking into the analyses the type of tobacco smoked did not alter results—there were still higher RR associated with smoking in women, particularly for smokers of cigarettes. However, as pointed out by Marang-van de Mheen and co-authors, the question of increased susceptibility cannot be discussed without discussing absolute versus relative risk. In their study they clearly demonstrate that although RR were similar in men and women, the absolute risk attributable to smoking was much higher in men. We can offer no simple explanation to the different findings in the two studies and for the moment are satisfied that smoking is deleterious for both genders.

References

1 Marang-van de Mheen PJ, Davey Smith G, Hart CL, Hole DJ. Are women more sensitive to smoking than men? Findings from the Renfrew and Paisley study. Int J Epidemiol 2001;30:787–92.[Abstract/Free Full Text]

2 World Health Organization. Tobacco or Health: A Global Status Report. Geneva: World Health Organization, 1997, pp.1–495.

3 Prescott E, Hippe M, Schnohr P, Hein HO, Vestbo J. Smoking and risk of myocardial infarction in women and men: longitudinal population study. Br Med J 1998;316:1043–47.[Abstract/Free Full Text]

4 Prescott E, Bjerg AM, Andersen PK, Lange P, Vestbo J. Gender difference in smoking effects on lung function and risk of hospitalization for COPD: results from a Danish longitudinal population study. Eur Respir J 1997;10:822–27.[Abstract/Free Full Text]

5 Prescott E, Osler M, Hein HO et al. Gender and smoking-related risk of lung cancer. Epidemiology 1998;9:79–83.[ISI][Medline]

6 Silverman EK, Weiss ST, Drazen JM et al. Gender-related differences in severe, Early-onset chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000;162:2152–58.[Abstract/Free Full Text]

7 Becklake MR, Kauffmann F. Gender differences in airway behaviour over the human life span. Thorax 1999;54:1119–38.[Free Full Text]

8 Xu X, Li B, Wang L. Gender difference in smoking effects on adult pulmonary function. Eur Respir J 1994;7:477–83.[Abstract/Free Full Text]

9 Seltzer CC. Framingham study data and ‘established wisdom’ about cigarette smoking and coronary heart disease. J Clin Epidemiol 1988; 42:743–50.[ISI]

10 Doll R, Gray R, Hafner B, Peto R. Mortality in relation to smoking: 22 years' observation on female British doctors. Br Med J 1980;280: 967–71.[ISI][Medline]

11 Njolstad I, Arnesen E, Lund Larsen PG. Smoking, serum lipids, blood pressure, and sex differences in myocardial infarction. A 12-year follow-up of the Finnmark Study. Circulation 1996;93: 450–56.[Abstract/Free Full Text]

12 McElduff P, Dobson A, Beaglehole R, Jackson R. Rapid reduction in coronary risk for those who quit cigarette smoking. Aust N Z J Public Health 1998;22:787–91.[ISI][Medline]

13 Woodward M, Moohan M, Tunstall-Pedoe H. Self-reported smoking, cigarette yields and inhalation biochemistry related to the incidence of coronary heart disease: results from the Scottish Heart Health Study. J Epidemiol Biostat 1999;4:285–95.[Medline]