Role of endogenous oestrogen in aetiology of coronary heart disease: analysis of age related trends in coronary heart disease and breast cancer in England and Wales and Japan
Role of endogenous oestrogen in aetiology of coronary heart disease:
analysis of age related trends in coronary heart disease and breast cancer in
England and Wales and Japan
Debbie A Lawlor, MRC research training fellow, Shah Ebrahim,
professor of epidemiology of ageing, George Davey Smith,
professor of clinical epidemiology.
Department of Social Medicine, University of Bristol, Bristol BS8 2PR
The sex difference in mortality from coronary heart disease decreases with
increasing age, suggesting a protective effectof oestrogen in
premenopausal women. This decrease is, however,the result of a
deceleration in death rates in men, with no changein rates in women
around the age of menopause.1 The age specificrate of breast cancera
condition associated with endogenous oestrogendoesshow a change around the age of menopause among women in the UnitedStates.2 The relatively low rates of coronary
heart diseasein premenopausal women may make it difficult to detect
an effectof the menopause.3 Rates of
breast cancer among Japanese womenare low. If low rates of coronary
heart disease around the timeof the menopause explain the lack of an
effect of the menopauseon age related trends then no effect of the
menopause on breastcancer trends among Japanese women might beexpected.
We obtained data on age specific mortality from coronary heart disease (ICD-9
(international classification of diseases, 9threvision): 410-414)
for women and men and from breast cancer (ICD-9:174) for women in
England and Wales from the Office for NationalStatistics and in
Japan from the World Health Organization. Wecalculated five year
aggregate rates for each country (1994-8for England and Wales and
1993-7 for Japan) and plotted them ona semilogarithmic
scale.
Coronary heart disease mortality in women from both countries increased with
age, and in both countries the death rate inmen decelerated at older
ages, reducing the magnitude of the sexdifference (figure). We found
no inflection in age specific mortalityfrom coronary heart disease
in women around the age of menopausein either England and Wales or
Japan. In contrast, mortality frombreast cancer began to decelerate
around the time of the menopausein both groups.
Age specific trends in mortality from
coronary heart disease in men and women and from breast cancer in women.
Aggregated data for England and Wales (top) and Japan (bottom)
Mortality from breast cancer in Japanese women is about half that from
coronary heart disease in women in England and Walesat ages 45-54;
it is thus unlikely that the low mortality fromcoronary heart
disease makes detection of a menopause effect difficult.The
inflection in breast cancer mortality occurs over a narrowage range,
suggesting that if effects of menopausal oestrogenon coronary heart
disease occurred they too should operate overa similar range and be
observable. However, coronary heart diseaseis associated with
several environmental risk factors, and ifthe effect of oestrogen on
risk of coronary heart disease is smallrelative to other risk
factors then any effect of the menopausemay bemasked.
Witteman et al argue that age related trends in coronary heart disease
mortality are not inconsistent with an effect of themenopause.4
They used simulation models based on levels ofrisk of coronary heart
disease in men to estimate age relatedtrends in "women who never
experience a menopause."4 Such analyses
are unrealistic andunhelpful.
Work on the aetiology of coronary heart disease in women has been dominated
by the idea that oestrogen plays an importantpart and is responsible
for the sex difference at younger ages.The implications of this are
that higher rates of coronary heartdisease in men are seen as
inevitable and that postmenopausalhormone replacement therapy has
become the mainstay of coronaryheart disease prevention in women. We
conclude that environmentalfactors are the most important
determinants of coronary heartdisease in women and men and of the
difference in coronary heartdisease rates between women and men.5
Acknowledgments
Contributors: All authors conceived the idea for the study. DAL undertook
the analysis and wrote the first draft of the paper. All authors contributed to
the final report. DAL will act as guarantor.
Footnotes
Funding: DAL is an MRC research training fellow and is funded by the Medical
Research Council. Views expressed are those ofthe
authors.
Meilahn E. Sex steroid hormonal influences on coronary
artery disease. In: Ness RB, Kuller LH, eds. Health and disease among
women. Oxford: Oxford University Press, 1999:155-182.
Lawlor DA, Ebrahim S, Davey Smith G. Sex matters: secular
and geographical trends in sex differences in coronary heart disease
mortality. BMJ 2001; 323: 541-545[Abstract/Full
Text].
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