Although no tumours have been observed in either species after 7 years, no conclusive evaluation can yet be made. 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.
Mestranol is embryolethal for pre- and postimplantation embryos in some species.
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'. 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.