Abstract

PIP: This monograph review of ethynodiol diacetate (ED) includes chemical and physical data (synonyms and tradenames), structural and molecular formulae and molecular weight of ED, chemical and physical properties (melting point, optical rotation and solubility), and the production, use, occurrence, and analysis of ED. Production of ED occurs via reduction of ethindrone to ethynodiol, which is then acetylated with acetic anhydride in pyridine to produce ED. ED is not known to occur naturally. Its applications in human medicine are similar to those of progesterone; it is primarily used in oral contraceptives combined with an estrogen and also is used to treat dysfunctional uterine bleeding, amenorrhea, and endometriosis; the French have used ED to treat advanced breast cancer. Analytical procedures for determining ED as a bulk chemical are presented tabularly. Biological data relevant to the evaluation of carcinogenic risk to humans are also presented in brief. In laboratory experiments, ED has been tested in mice, rats, and monkeys alone and in combination with an estrogen. ED produced mammary tumors in castrated male mice and in male rat. When combined with an estrogen, it increased the incidence of pituitary tumors in mice and of malignant mammary tumors in rats of both sexes. ED is reported to be embryolethal for pre- and postimiplantation embryos and to have teratogenic effects in some species. No human data are available except studies of combined oral contraceptives, the side effects of which may be ascribed to ED by implication. There is, therefore, limited evidence for the carcinogenicity of ED in animals, and ED may be associated with increased incidence of benign liver adenoma and decreased incidence of benign breast disease associated with oral contraceptives containing combined formulations.