Megestrol acetate
IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans 21: 431-439
1979
ISSN/ISBN: 0250-9555 PMID: 296136 Document Number: 449359
This monograph on megestrol acetate (MA) includes its chemical and physical data (synonyms and trade names), its structural and molecular formulae and molecular weight, chemical and physical properties (melting point, optical rotation, solubility, etc.), and its production, use, occurrence, and analysis. MA, which is not known to occur naturally, is produced by dehydrogenation of medroxyprogesterone acetate with chloranil. Its use in human medicine is for treatment of endometrial and breast carcinomas, as well as for treatment of acne, hirsutism, and sexual infantilism in females. Some countries, not including the U.S., use MA in combination oral contraceptive preparations. Typical analytical methods for determining the bulk chemical are presented tabularly. Biological data relevant to the evaluation of carcinogenic risk to humans are presented briefly. MA alone or with ethinyl estradiol has been tested in mice, rats, and dogs orally and in rats subcutaneously. Mammary tumors developed in dogs when treated with MA alone, and in mice when tested in combination with ethinyl estradiol. No case reports or human epidemiological studies of MA alone are available. It is concluded that there is limited evidence for the carcinogenicity of MA in dogs. In humans, oral contraceptives containing estrogens in combination with progestin have been related causally to an increased incidence of benign liver adenomas and a decreased incidence of benign breast disease.