An
IARC Monographs Working Group has concluded that combined
estrogen-progestogen oral contraceptives and combined
estrogen-progestogen menopausal therapy are carcinogenic to humans (Group 1), after a thorough review of the published scientific evidence.
At the same time, the Working Group stressed that there is also
convincing evidence that oral contraceptives have a protective effect
against some types of cancer.
There are both beneficial and adverse effects for oral contraceptives
and menopausal therapy. Each woman who uses these products should
discuss the overall risks and benefits with her doctor.
The Working Group, comprising 21 scientists from 8 countries, was
convened by the IARC Monographs Programme of the International Agency
for Research on Cancer (IARC), the cancer research agency of the World
Health Organization.
Major public health importance
"These new IARC Monographs [volume 91]
address exposures that are experienced daily by many millions of women
world-wide," said Dr Peter Boyle, Director of IARC. "It is of enormous
public health importance that we identify and understand the full range
of effects of these products." Worldwide, more than 100 million women –
about 10% of all women of reproductive age – currently use combined
hormonal contraceptives. In addition, there has been widespread use of
hormonal menopausal therapy: approximately 20 million women in
developed countries at its peak around the year 2000.
ORAL CONTRACEPTIVES INCREASE RISK OF SOME CANCERS AND DECREASE RISK OF OTHERS
Use of OC's increases risk of breast, cervix and liver cancer…
There
is a small increase in the risk of breast cancer in current and recent
users of oral contraceptives. However, ten years after cessation of
use, the risk appears to be similar to that in never-users. The risk of
cervical cancer increases with duration of use of combined oral
contraceptives. The risk of hepatocellular carcinoma is increased in
long-term users of combined oral contraceptives in populations with low
prevalences of hepatitis B infection and chronic liver disease – two
major causes of human liver cancer.
… but decreases risk of endometrial and ovarian cancer
In
contrast, the risks of endometrial and ovarian cancer are consistently
decreased in women who used combined oral contraceptives. The reduction
is generally greater with longer duration of use, and some reduction
persists at least 15 years after cessation of use.
More work needed to assess risks and benefits
Because
use of combined estrogen-progestogen contraceptives increases some
cancer risks and decreases risk of some other forms of cancer , it is
possible that the overall net public health outcome may be beneficial,
but a rigorous analysis is required to demonstrate this. This should be
done on a country-by-country basis and also consider the effects on
non-malignant diseases.
COMBINED MENOPAUSAL THERAPY INCREASES RISK OF CANCER
Breast cancer and endometrial cancer are increased
Epidemiological
studies consistently demonstrate an increased risk of breast cancer in
women who used combined menopausal therapy. Largely confined to current
or recent users, the risk increases with duration of use and exceeds
that in women taking estrogen-only therapy. Endometrial cancer risks
depend on the number of days that progestogens are included in the
combined therapy. When progestogens are taken fewer than 10 days per
month, the risk of endometrial cancer is increased, but when
progestogens are taken daily, the risk is similar to that in women who
never used hormonal therapy. There was not sufficient evidence to
conclude that hormonal therapy has a protective effect at any cancer
site.
Overall risks and benefits should be weighed carefully
Both
beneficial and adverse effects other than cancer have been established
for combined estrogen-progestogen menopausal therapy. As for oral
contraceptives, a rigorous risk/benefit analysis would be useful to put
the different effects in perspective and assess the overall
consequences for public health.
WHAT IS NEW, AND WHAT DOES THIS MEAN FOR ME?
More cancer sites are targets of oral contraceptives
Previously, combined oral contraceptives had been determined to be
carcinogenic to humans, but only primary liver cancer was specifically
implicated. The Working Group concluded that combined oral
contraceptives alter the risk of several common cancers in women. They
increase a woman's risk of cervical cancer, breast cancer, and liver
cancer. At the same time, they have a protective effect against
endometrial cancer and ovarian cancer.
Menopausal therapy now "Carcinogenic to humans"
Previously, combined menopausal therapy was regarded as "possibly
carcinogenic to humans." The new evaluation concluded, based on an
expanded study base, that it is carcinogenic to humans, increasing a
woman's risk of breast cancer and, when progestogens are taken fewer
than 10 days per month, endometrial cancer.
Consider risks and benefits of hormonal products and use only under careful medical supervision
This
new information about cancer risks – and also protection against cancer
in the case of oral contraceptives – makes it important that each woman
who uses these hormonal products discuss the risks and benefits with
her doctor, taking into consideration her personal circumstances and
family history of cancer and other diseases.
ABOUT THE IARC MONOGRAPHS
What are the IARC Monographs?
The
IARC Monographs critically review and evaluate the published scientific
evidence on human carcinogenic hazards. These include chemicals,
complex mixtures, occupational exposures, lifestyle factors, and
physical and biological agents. International, interdisciplinary
working groups of expert scientists prepare the critical reviews and
consensus evaluations. Nearly 400 potentially carcinogenic agents and
exposures have been identified in the 91 volumes and approximately 900
evaluations developed since 1971. National and international health
agencies use the IARC Monographs as a source of scientific information
and as the scientific basis for their efforts to prevent cancer.
Definitions
- Group 1: The agent (mixture) is carcinogenic to humans.
The exposure circumstance entails exposures that are carcinogenic to humans.
This category is used when there is sufficient evidence
of carcinogenicity in humans. Exceptionally, an agent (mixture) may be
placed in this category when evidence of carcinogenicity in humans is
less than sufficient but there is sufficient evidence of
carcinogenicity in experimental animals and strong evidence in exposed
humans that the agent (mixture) acts through a relevant mechanism of
carcinogenicity.
This
category includes agents, mixtures and exposure circumstances for
which, at one extreme, the degree of evidence of carcinogenicity in
humans is almost sufficient, as well as those for which, at the other
extreme, there are no human data but for which there is evidence of
carcinogenicity in experimental animals. Agents, mixtures and exposure
circumstances are assigned to either group 2A (probably carcinogenic to
humans) or group 2B (possibly carcinogenic to humans) on the basis of
epidemiological and experimental evidence of carcinogenicity and other
relevant data.
- Group 2A: The agent (mixture) is probably carcinogenic to humans.
The exposure circumstance entails exposures that are probably carcinogenic to humans.
This category is used when there is limited evidence of carcinogenicity in humans and sufficient evidence of carcinogenicity in experimental animals. In some cases, an agent (mixture) may be classified in this category when there is inadequate evidence of carcinogenicity in humans and sufficient evidence
of carcinogenicity in experimental animals and strong evidence that the
carcinogenesis is mediated by a mechanism that also operates in humans.
Exceptionally, an agent, mixture or exposure circumstance may be
classified in this category solely on the basis of limited evidence of carcinogenicity in humans.
- Group 2B: The agent (mixture) is possibly carcinogenic to humans.
The exposure circumstance entails exposures that are possibly carcinogenic to humans.
This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence
of carcinogenicity in experimental animals together with supporting
evidence from other relevant data may be placed in this group.
- Group 3: The agent (mixture or exposure circumstance) is not classifiable as to its carcinogenicity to humans.
This category is used most commonly for agents, mixtures and exposure circumstances for which the evidence of carcinogenicity is inadequate in humans and inadequate or limited in experimental animals
Exceptionally, agents (mixtures) for which the evidence of carcinogenicity is inadequate in humans but sufficient
in experimental animals may be placed in this category when there is
strong evidence that the mechanism of carcinogenicity in experimental
animals does not operate in humans.
- Group 4: The agent (mixture) is probably not carcinogenic to humans.
This category is used for agents or mixtures for which there is evidence suggesting lack of carcinogenicity in humans and in experimental animals. In some instances, agents or mixtures for which there is inadequate evidence of carcinogenicity in humans but evidence suggesting lack of carcinogenicity
in experimental animals, consistently and strongly supported by a broad
range of other relevant data, may be classified in this group.
The
vol. 91 of the Monograph series, on COMBINED ORAL CONTRACEPTIVES AND
MENOPAUSAL THERAPY will be available some time early next year. See http://monographs.iarc.fr/ for more details then.
FOR FURTHER INFORMATION
Contact Dr Nicolas Gaudin, Chief of IARC Communications, at
com@iarc.fr
. The Working Group's summary on this topic will soon appear on the IARC Monographs website (http://monographs.iarc.fr). More details available in the August issue of The Lancet Oncology (http://oncology.thelancet.com).
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