IARC MONOGRAPHS PROGRAMME
FINDS COMBINED ESTROGEN-PROGESTOGEN CONTRACEPTIVES AND MENOPAUSAL
THERAPY ARE CARCINOGENIC TO HUMANS
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.
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.
Group
2
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
sufficientevidence 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
limitedevidence 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 ofcarcinogenicity in humans and in experimental animals. In some
instances, agents or mixtures for which there is inadequate
evidence of carcinogenicity in humans but evidence suggestinglack 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
. 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/).
For questions and comments regarding our mission and products, please contact
us.
)
