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


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

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