International Agency for Research on Cancer (IARC) - Summaries & Evaluations
DIETHYLSTILBOESTROL (STILBOESTROL)
VOL.: 6 (1974) (p. 55)
5. Summary of Data Reported and Evaluation
(N.B.: This section should be read in conjunction with the section
'General Conclusions on Hormones'.)
5.1 Animal carcinogenicity data
Diethylstilboestrol (DES) was tested in mice by oral administration,
local application and subcutaneous injection, in mice, rats, hamsters
and squirrel monkeys by subcutaneous implantation and in hamsters by
subcutaneous injection. Its administration to mice resulted in an
increased incidence of mammary and lymphoid tumours in both males and
females, and of interstitial-cell tumours of the testis in males and
cervical and vaginal tumours in females, including those exposed only
on the first day of life. In rats, increased incidences of pituitary,
mammary and bladder tumours were observed. In hamsters, a high
incidence of renal tumours was observed in castrated males and females
and in intact males, but not in intact females. In squirrel monkeys,
malignant mesotheliomas of the uterine serosa were observed.
DES treatment in most cases increased the incidence of mammary tumours
in strains of mice having a spontaneous incidence of these tumours,
which may be related to the presence of a virus; testicular tumours
occurred in strains having a particular genetic susceptibility to
such tumours. No evidence of a possible role of a virus has been shown
in rats. Bladder tumours occurred only in rats in which bladder
calculi were present.
In most cases, an accurate assessment of the effective carcinogenic
dose in implantation studies is not possible. However, in oral
administration studies, the lowest statistically significant dose
(p < 0.01) producing mammary carcinomas in mice was about 0.15
mg/day (6 mg/kg bw/day). This dose is similar to that
used in humans in the control of menopausal symptoms by DES (10
mg/kg bw/day) and 30 times less than the dose given for the
control of mammary or prostatic cancer (300 mg/kg bw/day).
5.2 Human carcinogenicity data
The administration of diethylstilboestrol to women during pregnancy is
associated with an increased risk of vaginal or cervical
adenocarcinoma in their exposed female offspring. There may also be an
increased risk of endometrial carcinoma in women with gonadal
dysgenesis treated with this drug. It is possible that the
administration of the drug therapeutically to men with carcinoma of
the prostate increases the risk of breast cancer.
Subsequent evaluations: Vol. 21 (1979);
Suppl. 7 (1987)
Last updated: 17 March 1998