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

NORETHISTERONE AND NORETHISTERONE ACETATE

VOL.: 21 (1979) (p. 441)

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

Norethisterone and its acetate alone or in combination with oestrogens were tested in mice, rats and dogs by oral administration and in mice by subcutaneous implantation. When administered alone to mice, norethisterone increased the incidence of benign liver-cell tumours in males and of pituitary tumours in females and produced granulosa-cell tumours of the ovary in females. Administration of norethisterone acetate alone increased the incidence of benign liver-cell tumours in male mice. In male rats, administration of norethisterone alone increased the incidence of benign liver-cell tumours.

Norethisterone in combination with mestranol, or the acetate in combination with ethinyloestradiol, increased the incidence of pituitary tumours in mice of both sexes; norethisterone in combination with ethinyloestradiol increased the incidence of pituitary tumours in female mice. In combination with mestranol it increased the incidence of benign liver-cell tumours in male rats and of malignant mammary tumours in animals of both sexes. Norethisterone acetate in combination with ethinyloestradiol increased the incidence of benign mammary tumours in male rats in one study and increased the incidence of benign liver-cell and mammary tumours in rats of both sexes in a further study.

A study in dogs in which it was given in combination with ethinyloestradiol is still in progress.

Norethisterone is embryolethal in some species and produces virilization in female foetuses.

5.2 Human data

No case reports or epidemiological studies on norethisterone or norethisterone acetate 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 norethisterone and of its acetate in 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






















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