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FERTILITY DRUGS AND
GYNECOLOGIC CANCER
ROBAB DAVAR M.D.
1388
Ovarian cancer :

The use of fertility drugs has been
associated with neoplasia, particularly
borderline ovarian tumors, in some but
not all, studies .Studies to date have
focused on clomiphene and gonadotropin
therapy.
 In one series, the risk appeared to be only in
women who had undergone more than 12
cycles of clomiphene citrate therapy .
 The apparent association between fertility
drug use and epithelial ovarian cancer appears
to be related to the fact that these drugs are
more likely to be used in infertile women, who
are known to be at higher risk of developing
ovarian cancer, irrespective of their use of
fertility drugs .
 Because of the observations that pregnancy
rates are low after six cycles of treatment,
and that 12 or more cycles may increase the
risk of ovarian neoplasms , the American
College of Obstetricians and Gynecologists
has suggested that clomiphene treatment be
limited to fewer than 12 cycles, and that the
number of gonadotropin cycles be
minimized as well .
Breast cancer
 There does not appear to be an increased
risk of breast cancer in women treated with
fertility drugs.
 However, interpretation of the available
data is limited by several factors, such as
survey information, small subgroup
numbers, lack of evaluation by drug
type/dose or cause of infertility, and
confounding by the presence of other risk
factors for breast cancer.
 One relatively large case-control study
showed that infertile women with breast
cancer were more likely to have been
treated with human menopausal
gonadotropin (hMG) for more than six
cycles than infertile women without breast
cancer; no increased risk was noted for
clomiphene citrate. However, this study was
subject to many of the limitations noted
above.
 Women taking infertility drugs can be
reassured that these drugs probably do not
increase their risk of breast cancer,
although it is not clear whether some
subgroups may be at increased risk.
Further investigation is required.
Uterine cancer
 In a retrospective, cohort study, neither
clomiphene nor gonadotropin use appeared
to be associated with an increased risk of
melanoma, thyroid, cervical, or colon
cancers .
 In contrast, the same investigators reported
that clomiphene use may be associated with
a greater risk of endometrial cancer.
However, one explanation for these findings
is that infertile women who used
clomiphene were more likely to have
underlying chronic anovulation, which is a
strong risk factor for development of
endometrial cancer, than infertile women
not exposed to clomiphene.
 Other ovulation induction therapies
(including pulsatile GnRH, and dopamine
agonists) have not been linked to ovarian or
breast cancer risk.