world cancer report - iarc
world cancer report - iarc
world cancer report - iarc
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REPRODUCTIVE FACTORS AND HORMONES<br />
SUMMARY<br />
>Female sex steroid hormone metabolism,<br />
reproductive factors and menopausal<br />
status affect the development of<br />
endometrial, ovarian and breast <strong>cancer</strong>.<br />
>Use of combined oral contraceptives<br />
accounts for a slight increase in risk of<br />
breast <strong>cancer</strong>, but is protective against<br />
ovarian and endometrial <strong>cancer</strong>s.<br />
> Hormone replacement therapy is associated<br />
with increases in risk of breast and<br />
endometrial <strong>cancer</strong>s, but may relieve<br />
other health problems associated with<br />
menopause.<br />
> Energy imbalance due to a Western<br />
lifestyle causes increased serum levels<br />
of insulin-like growth factor I (IGF-I)<br />
which is predictive of an elevated risk<br />
for prostate <strong>cancer</strong>.<br />
There is overwhelming evidence that sex<br />
steroids (androgens, estrogens, progestogens)<br />
can have an important role in the<br />
development of human tumours, especially<br />
of the female reproductive organs<br />
(endometrium, ovary) and breast.<br />
Cancers of the breast, endometrium<br />
and ovary<br />
For breast <strong>cancer</strong>, incidence rates rise<br />
more steeply with age before menopause<br />
than after, when ovarian synthesis of<br />
estrogens and progesterone ceases and<br />
ovarian androgen production gradually<br />
diminishes. Furthermore, breast <strong>cancer</strong><br />
risk is increased in women who have early<br />
menarche, or who have late menopause,<br />
whereas an early age at first full-term<br />
pregnancy and high parity are associated<br />
with reduced risk of the three forms of<br />
<strong>cancer</strong> [1]. The rise in incidence rates of<br />
endometrial <strong>cancer</strong> also appears to flatten<br />
off at older age, but this change is related<br />
76 The causes of <strong>cancer</strong><br />
less markedly to the menopausal transition<br />
than is the case with breast <strong>cancer</strong>.<br />
Ovarian <strong>cancer</strong> risk does not show strong<br />
relationships with menstrual history, but is<br />
clearly and inversely related to parity [2].<br />
Obesity (related to various alterations in<br />
plasma levels of total and bioavailable sex<br />
steroids) is a strong risk factor for<br />
endometrial <strong>cancer</strong>, as well as for breast<br />
<strong>cancer</strong> in postmenopausal women.<br />
Circulating levels of sex steroids are regulated<br />
by a range of factors, including<br />
insulin and insulin-like growth factors<br />
(IGFs), which thus provide a possible link<br />
between many observations regarding<br />
excessive energy intake and increased<br />
risk of <strong>cancer</strong> (Box: IGF-1 and <strong>cancer</strong>,<br />
p79). Together, these observations suggest<br />
that alterations in endogenous sex<br />
steroid metabolism, and notably the ovarian<br />
synthesis of sex steroids, can be an<br />
important determinant of risk for each of<br />
the three forms of <strong>cancer</strong> in women.<br />
Breast <strong>cancer</strong> risk is increased in postmenopausal<br />
women with a hyperandrogenic<br />
(excess of androgens) plasma hormone<br />
profile, characterized by increased<br />
plasma levels of testosterone and ∆-4<br />
androstenedione, reduced levels of sex<br />
hormone-binding globulin and increased<br />
levels of total estradiol, and bioavailable<br />
estradiol not bound to sex hormone-binding<br />
globulin [e.g. 3-5]. Similarly, postmenopausal<br />
women are at increased risk<br />
from endometrial <strong>cancer</strong>. The situation for<br />
breast <strong>cancer</strong> in premenopausal women is<br />
less clear [6,7].<br />
Oral contraceptives<br />
Oral contraceptives, in the form of estrogen-progestogen<br />
combinations, were<br />
introduced in the early 1960s, and rapidly<br />
found very widespread use in most developed<br />
countries. Over 200 million women<br />
are estimated to have used oral contraceptives<br />
since their introduction and<br />
about 60 million women are currently<br />
using them [8].<br />
Preparations of oral contraceptives have<br />
undergone substantial changes over time,<br />
including reductions in the potency and<br />
dosage of the estrogens, addition of different<br />
progestogens (progesterone analogues),<br />
and introduction (in 1983) of<br />
biphasic and triphasic pills that vary in<br />
the amounts of estrogen and progestogen<br />
throughout the month. A progestogenonly<br />
pill (“minipill”) was first marketed in<br />
the USA in 1973, but has never been used<br />
widely. Sequential pills, with two weeks of<br />
estrogen alone followed by a combination<br />
of estrogen and progestogen for five days,<br />
were removed from the consumer market<br />
in the 1970s after concern about a possible<br />
association with endometrial <strong>cancer</strong>.<br />
There is a small increase in the risk of<br />
breast <strong>cancer</strong> in current and recent users<br />
of combined oral contraceptives containing<br />
both estrogen and progestogen [8].<br />
This association, however, is unrelated to<br />
duration of use or type and dose of<br />
preparation and, 10 years after cessation<br />
of use, is no longer present (Fig. 2.71).<br />
The association of breast <strong>cancer</strong> with oral<br />
contraceptive use may be a result of<br />
detection bias, due to increased attention<br />
to the occurrence of breast tumours in<br />
women regularly visiting a physician for<br />
contraceptive prescriptions.<br />
Risk of endometrial <strong>cancer</strong> is approximately<br />
halved in women using combination-type<br />
oral contraceptives, the reduction<br />
in risk being stronger the longer the<br />
contraceptives are used [8]. The reduction<br />
in risk persists for at least ten years<br />
Fig. 2.70 Varieties of oral contraceptives. Use of<br />
the contraceptive pill reduces the risk of <strong>cancer</strong>s<br />
of the ovary and endometrium, but is associated<br />
with a slightly increased risk of breast <strong>cancer</strong>.