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
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'.
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