International Agency for Research on Cancer (IARC) - Summaries & Evaluations
MESTRANOL
VOL.: 21 (1979) (p. 257)
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
Mestranol was tested in mice, rats, dogs and monkeys by oral
administration; in most studies it was administered in combination
with progestins. When administered alone, it increased the incidences
of pituitary tumours in both sexes of one strain of mice and increased
the incidence of malignant mammary tumours in castrated males of two
further strains and in males and females of another strain. It also
produced an increased incidence of malignant mammary tumours in female
rats.
Studies in dogs and monkeys are still in progress. Although no
tumours have been observed in either species after 7 years, no
conclusive evaluation can yet be made.
In experiments in which mestranol was administered to female mice in
combination with norethynodrel, pituitary tumours and vaginal and
cervical squamous-cell carcinomas were produced; in male mice, an
increased incidence of mammary tumours was observed following
administration of mestranol in combination with norethynodrel or
ethynodiol diacetate. Combinations with norethynodrel or
norethisterone resulted in an excess of benign liver-cell tumours in
male rats and increased the incidence of malignant mammary tumours in
rats of both sexes.
In dogs, administration of combinations with various synthetic
progestins led to the formation of mammary tumours. In monkeys given
these combinations as well as combinations with norethynodrel or
ethynodiol diacetate, no mammary nodules were observed after 5 and 7
years of experimentation, respectively. These experiments are still in
progress.
It was also tested in combination with norethynodrel by subcutaneous
administration in mice, rats and hamsters; it produced an increased
incidence of mammary tumours in female mice.
Mestranol is embryolethal for pre- and postimplantation embryos in
some species.
5.2 Human data
No case reports or epidemiological studies on mestranol 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 sufficient evidence for the carcinogenicity of mestranol in
experimental animals. In the absence of adequate data in humans, it is
reasonable, for practical purposes, to regard mestranol as if it
presented a carcinogenic risk to humans. The use of oral
contraceptives containing mestranol 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 mestranol 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 (1987) (Steroidal oestrogens)
Last updated: 7 April 1998