International Agency for Research on Cancer (IARC) - Summaries & Evaluations
VOL.: 21 (1979) (p. 233)
5. Summary of Data Reported and Evaluation
(N.B. - This section should be read in conjunction with the General Remarks on Sex Hormones and with
the General Conclusions on Sex Hormones.)
5.1 Experimental data
Ethinyloestradiol was tested in mice, rats, dogs and monkeys by oral
administration and in rats by subcutaneous injection; in most studies
it was administered in combination with progestins.
When administered alone to mice, it increased the incidence of
pituitary tumours and malignant mammary tumours in both males and
females and produced malignant tumours of the uterus and its cervix in
females. In rats, it increased the incidence of benign liver-cell
tumours in both males and females and produced malignant liver-cell
tumours in females.
When ethinyloestradiol was given in combination with certain
progestins, excess incidences of malignant tumours of the uterine
fundus were observed in female mice and of benign and/or malignant
mammary tumours in male rats; in female rats, the combinations reduced
but did not prevent the incidence of malignant liver-cell tumours when
compared with that produced by ethinyloestradiol alone. In dogs, no
tumours that could be attributed to the treatment were found. The
study in monkeys was still in progress at the time of reporting: no
tumours had been found after 5 years of observation.
Mammary fibroadenomas were produced in female rats following
subcutaneous injection of a combination of ethinyloestradiol with
Ethinyloestradiol is embryolethal for preimplantation embryos in some
5.2 Human data
No case reports or epidemiological studies on ethinyloestradiol alone
were available to the Working Group. Epidemiological studies on steroid
hormones used in oestrogen-progestin contraceptive preparations have been summarized
in the section, 'Oestrogens and Progestins in Relation to Human Cancer'.
There is sufficient evidence for the carcinogenicity of
ethinyloestradiol in experimental animals. In the absence of adequate
data in humans, it is reasonable, for practical purposes, to regard
ethinyloestradiol as if it presented a carcinogenic risk to humans.
The use of oral contraceptives containing ethinyloestradiol in
combination with progestins has been related causally to an increased
incidence of benign liver adenomas and a decreased incidence of benign
breast disease. Studies also strongly suggest that the administration
of oestrogens is causally related to an increased incidence of
endometrial carcinoma; there is no evidence that ethinyloestradiol is
different from other oestrogens in this respect.
For definition of the italicized terms, see Preamble Evaluation.
Previous evaluation: Vol. 6 (1974)
Subsequent evaluation: Suppl. 7 (Steroidal oestrogens)
Last updated: 6 April 1998