Hall NF, Gale CR, Syddall H, Phillips DI, Martyn CN. Risk of macular
international classification and grading system for age-related maculo-
McCarty CA, Mukesh BN, Guymer RH, Baird PN, Taylor HR.
In t' Veld BA, Ruitenberg A, Hofman A, Launer LJ, van Duijn CM, Stijnen
Cholesterol-lowering medications reduce the risk of age-related
T, et al. Nonsteroidal anti-inflammatory drugs and the risk of Alzheimer's
maculopathy progression. Med J Aust 2001;175:340.
disease. N Engl J Med 2001;345:1515-21.
Arnold JJ, Sarks SH. Extracts from "clinical evidence": age related macu-lar degeneration. BMJ 2000;321:741-4.
Bird AC, Bressler NM, Bressler SB, Chisholm IH, Coscas G, Davis MD, etal, for the International ARM Epidemiological Study Group. An
Mortality from cardiovascular disease more than 10 years after radiotherapy for breast cancer: nationwide cohort study of 90 000 Swedish women Increased
During radiotherapy for breast cancer there is often
with previously registered cancers (except squamous
some irradiation of the heart and major blood vessels,
cell skin cancer), 89 407 women aged 18-79 with
which could increase cardiovascular mortality many
unilateral breast cancer remained. We stratified
years later.1-3 The dose of radiation to the heart is
analyses of subsequent mortality in groups of five
10 years after
generally higher when the left rather than the right
years by calendar year of diagnosis, time since
breast is affected. Therefore, indirect evidence on the
diagnosis, and age at diagnosis. Stratification by age
magnitude of any risk is available where the tumour
was necessary because the proportion of left sided
laterality (left or right breast) can be linked to
tumours increases with age.5 Each woman's
subsequent cardiovascular mortality.1 2 Studies of the
contribution to the person years at risk ran from the
survivors of the atomic bombing of Japan who
date of diagnosis until her date of death, date of
received single doses to the whole body of 0-4 Gy
emigration, 100th birthday, or 1 January 1997,
show that the cardiovascular disease risk is dose
whichever was earliest. We used Poisson regression to
related and increases by about 14% per gray.4
calculate mortality ratios, left versus right, from the
numbers of deaths and person years. Ratios greater
Participants, methods, and results
than one indicate greater mortality in women with left
sided tumours than in women with right sided
Since 1970, the nationwide Swedish cancer registry
has recorded the laterality of breast cancers but not
Mortality from breast cancer was identical in
the use of radiotherapy. Unpublished data from
women with left sided or right sided tumours (table).
regional Swedish registries suggest that about 30% of
Mortality from cardiovascular diseases was higher in
women with early breast cancer during the 1970s and
women with left sided tumours. Little excess occurred
early '80s received radiotherapy. We linked registry
in the first 10 years after diagnosis (mortality ratio
records (1970-96) with national mortality records. The
1.01; 95% confidence interval 0.96 to 1.07), but later
study was approved by the ethics committee of the
the ratio was 1.10 (1.03 to 1.18; P=0.004), 1.13 (1.03 to
1.25; P=0.01) for ischaemic heart disease (half of all
cardiovascular mortality), and 1.08 (0.98 to 1.18) for
diagnosed at autopsy or outside Sweden and those
other cardiovascular deaths (about 30% of which
Karolinska Institute,171 77 Stockholm,Sweden
Mortality ratio for women with left sided breast cancer versus women with right sided breast cancer during and after the first 10 years
from diagnosis of breast cancer among 89 407 women registered during 1970-96 at the Swedish cancer registry
All years <10 years
>10 years Mortality ratio, left Mortality ratio, left Mortality ratio, left Cause of death (ICD-9 code) versus right (95% CI) versus right (95% CI) versus right (95% CI)
ICD-9=International classification of diseases, ninth revision. *P=0.04†P
BMJ VOLUME 326 1 FEBRUARY 2003 bmj.com
probably involved heart disease). For the remaining
ratio of 1.10 is, however, wide, so the true
causes, mortality in women with left sided tumours
cardiovascular hazard from radiotherapy in the 1970s
did not differ significantly from that in women with
Contributors: The study was conceived and designed by PH, SD,
Most of the late cardiovascular deaths involved
AE, and FG. The statistical analysis was designed by SD and
women treated for breast cancer in the 1970s, and
PMcG and done by PMcG. All authors contributed to the
improvements in radiotherapy techniques since then
interpretation of the results and the preparation of the
have tended to reduce radiation dose to the heart. For
manuscript. PH is guarantor for the data; SD and PMcG are
guarantors for the statistical analysis.
cardiovascular ratio, left versus right, was still 1.11 but
Funding: Clinical Trial Service Unit (SD, PMcG, and RP)supported by Cancer Research UK, the Medical Research
with a wide 95% confidence interval (0.95 to 1.29).
Council, and the British Heart Foundation. Karolinska Institute(FG, AE, and PH) supported by independent Swedish research
foundations, government sources, and the European Union. Competing interests: None declared.
A mortality ratio, left versus right, of 1.10 forcardiovascular disease more than 10 years after
Paszat L, Mackillop WJ, Groome PA, Boyd C, Schulze K, Holowaty E. Mortality from myocardial infarction after adjuvant radiotherapy for
diagnosis of breast cancer is compatible with a
breast cancer in the surveillance, epidemiology and end-results cancer
substantial hazard among some of those actually
registries. J Clin Oncol 1998;16:2625-31.
Rutqvist LE, Johansson H. Mortality by laterality of the primary tumour
irradiated. For example, if about 30% of women
among 55 000 breast cancer patients from the Swedish Cancer Registry.
surviving 10 years after breast cancer had been
irradiated then a cardiovascular mortality ratio of 1.10
Early breast cancer trialists' collaborative group (EBCTCG). Favourableand unfavourable effects on long-term survival of radiotherapy for early
in all women and 1.00 in unirradiated women would
suggest a ratio of 1.33 in those irradiated. This could
Shimizu Y, Pierce DA, Preston DL, Mabuchi K. Studies of the mortality of
be produced by a 60% increase in late cardiovascular
atomic bomb survivors: non-cancer mortality 1950-1990. Radiat Res
mortality after irradiation for a left sided tumour and
Weiss HA, Devesa SS, Brinton LA. Laterality of breast cancer in the
a 20% increase after irradiation for a right sided
United States. Cancer Causes Control 1996;7:539-43.
tumour. The confidence interval for the observed
Thromboembolism associated with the new
A 35 year old woman had pulmonary thrombosis
17 days after she started taking the contraceptive.
She had given birth four months earlier.
Ethinylestradiol with drospirenone has been
Our centre, the Dutch spontaneous reporting system for
approved as an oral contraceptive in all European Union
adverse drug reactions, recently received five reports of
countries since 2000 and has recently been launched in
thromboembolism as a suspected adverse drug reaction
the United Kingdom.2 The public assessment report of
to the new oral contraceptive Yasmin (ethinylestradiol
the contraceptive gives only one suspected case of
pulmonary embolism but also says that the number of
A 17 year old woman suddenly collapsed and died
cases in the preregistration studies are too low for a
after taking the contraceptive for six months. Autopsy
showed that she had had a massive pulmonary embolism.
No obvious risk factors for thromboembolism, such as
The risk of thromboembolism for women using the
smoking, a period of long immobilisation, air flights, or
third generation (combined) pill has long been debated.
concomitant medication, were evident.1 Because she died
Physicians therefore may prefer a new type of combined
suddenly no blood sample was taken. Blood taken from
pill, like ethinylestradiol with drospirenone, assuming
her parents did not test positive for any of the known risk
that these are safer. However, an association of these
factors: concentrations of protein C and antithrombin III
drugs with a lower risk of thromboembolism has not
were normal. The activated partial thromboplastin time
been proved by research, and our cases show that newer
and partial thromboplastin time were normal, and the
contraceptive pills may have a risk of thromboembolism.
existence of factor V Leiden mutation was excluded.
At present, insufficient data on the superiority of
A 28 year old woman changed her oral contraceptive
ethinylestradiol with drospirenone are available.
from ethinylestradiol with desogestrel (Marvelon) to
ethinylestradiol with drospirenone. Four months later shehad thrombosis in one leg and was treated with
acenocoumarol. Risk factors or concomitant drugs wereunknown.
Winkler UH. Oral contraception in women at risk of venous disease.
Another patient, a 45 year old woman, had deep vein
thrombosis in one leg after taking ethinylestradiol with
Sheldon T. Dutch GPs warned against new contraceptive pill. BMJ2002;324:869.
drospirenone for two months, as did a 50 year old
Official site of Dutch medicines evaluation board. www.cbg-meb.nl/nl/docs/
woman who took the contraceptive for three months.
gnsmiddl/par-yasmin.pdf (accessed 21 October 2002). BMJ VOLUME 326 1 FEBRUARY 2003 bmj.com
TREATMENT OF INFERTILITY An Integrative Approach José Choy, MD; Natália R. Cordeiro, PhD. Associação Portuguesa de Acupunctura e Disciplinas Associadas Abstract Infertility is a new emerging problem in modern societies. Since II World War, History has been changing the meaning of reproductive success, enhancing the value of procreation in industrialized countries. Benedicti
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