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'.
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
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