Abstract

PIP: This monograph on chlormadinone acetate (CA) includes chemical and physical data (synonyms and trade names), structural and molecular formulae and molecular weight of CA, chemical and physical properties of CA, and the production, use, occurrence, and analysis of CA. Production of CA, which is not known to occur naturally, occurs by treatment of 17-acetoxyprogesterone with ethyl orthoformate in the presence of an acid catalyst to produce the 3-enol ether of the corresponding 3,5-dione. Typical analytical procedures for determining CA as a bulk chemical are summarized tabularly. CA, before suspension from commercial use, was marketed as an ingredient in sequential oral contraceptives. It is approved as an estrus regulator in cattle feed. Biological data relevant to the evaluation of carcinogenic risk to humans are presented in brief. Experimental work with dogs, mice, and rats using oral administration has been done. When CA is combined with mestranol and given to mice, it increases the incidence of pituitary tumors in both sexes; combined with ethinylestradiol it increased the incidence of mammary tumors. When CA was given alone to dogs, mammary tumors developed. No human case reports or epidemiological studies on CA alone are available. Hence, it was concluded that there is limited evidence for the carcinogenicity of CA in dogs. In humans, oral contraceptives containing estrogens in combination with progestins have been related causally to increased incidence of benign liver adenomas and decreased incidence of benign breast disease, and so CA is implicated in this respect.