PIP: This monograph on ethinyloestradiol (EE) includes chemical and physical data (synonyms and trade names), structural and molecular formulae and molecular weight of the substance, chemical and physical properties of EE, and the production, occurrence, use, and analysis of EE. Production of EE, which has not been reported to occur naturally, occurs by treatment of estrone with potassium acetylide in liquid ammonia. EE is 1 of the most active estrogens known when administered orally; it is used in human medicine for 1) estrogen replacement therapy, 2) functional menstrual disorders, 3) postpartum breast engorgement, 4) dysfunctional uterine bleeding, 5) prostatic carcinoma, and 6) for advanced breast cancer in postmenopausal women. Its largest use is as an oral contraceptive, administered in combination therapy with a progestin. Typical analytical methods for EE are presented tabularly. Biological data relevant to the evaluation of carcinogenic risk to humans are presented in brief. Mice, rats, dogs, and monkeys have been used in experiments of EE by the oral route, and rats have been studied using subcutaneous injection. When administered alone, EE increased the incidence of pituitary tumors and malignant mammary tumors in both sexes and malignant cervical and vaginal tumors in females. Rats showed increased incidence of benign liver tumors in both sexes and malignant liver tumors in females. When combined with a progestin, EE produced mammary fibroadenomas in female rats, via subcutaneous infection. EE is embryolethal for preimplantation embryos in some species. Therefore, there is sufficient evidence for the carcinogenicity of EE in experimental animals. No human studies were available on EE alone, but since it is used in combined oral contraceptives, carcinogenic risks associated with these are associated causally with EE.