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 megestrol acetate.

Ethinyloestradiol is embryolethal for preimplantation embryos in some species.

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'.

5.3 Evaluation

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

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