International Agency for Research on Cancer (IARC) - Summaries & Evaluations


VOL.: 21 (1979) (p. 461)

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

Norethynodrel was tested in mice, rats and monkeys alone or in combination with mestranol by oral administration. It was also tested alone in mice by subcutaneous implantation, and in combination with mestranol in mice, rats and hamsters by subcutaneous injection.

When given alone, norethynodrel increased the incidence of pituitary tumours in mice of both sexes and of mammary tumours in castrated males of one strain; it also increased the incidence of liver-cell, pituitary and mammary tumours in male rats.

When given in combination with mestranol, it increased the incidence of pituitary, mammary, vaginal and cervical tumours in female mice, of pituitary tumours in male mice, of mammary tumours in castrated male mice, of benign liver-cell tumours in male rats and of malignant mammary tumours in rats of both sexes. The study in hamsters was of too short duration to be considered for evaluation.

Oral administration of norethynodrel in combination with mestranol to Macaca mulatta monkeys for 5 years did not increase the incidence of mammary tumours; the study is still in progress.

Norethynodrel was reported to be embryolethal in some species and to have teratogenic effects in mice.

5.2 Human data

No case reports or epidemiological studies on norethynodrel alone were available to the Working Group. Epidemiological studies on steroid hormones used in oestrogen-progestin oral contraceptive preparations have been summarized in the section, 'Oestrogens and Progestins in Relation to Human Cancer'.

5.3 Evaluation

There is limited evidence for the carcinogenicity of norethynodrel alone and in combination with mestranol in experimental animals. In humans, oral contraceptives containing oestrogens in combination with progestins have been related causally to an increased incidence of benign liver adenomas and a decreased incidence of benign breast disease.

For definition of the italicized terms, see Preamble Evaluation.

Previous evaluation: Vol. 6 (1974)

Subsequent evaluation: Suppl. 7 (1987) (Progestins; combined oral contraceptives)

Last updated: 7 April 1998

    See Also:
       Toxicological Abbreviations
       Norethynodrel (IARC Summary & Evaluation, Volume 6, 1974)