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Abstract
Premarin, a complex of conjugated equine estrogens manufactured by Wyeth for use as hormone replacement therapy in women, was originally developed by the Canadian pharmaceutical firm Ayerst, McKenna and Harrison. The name Premarin was coined from pregnant mare urine, from which the estrogen complex was isolated. Although the complete composition of Premarin and its active components remains undisclosed or unknown, Wyeth reports that it contains a mixture of 10 estrogens. The history of Premarin is entangled in a fascinating story of human intrigue involving ingenuity, influence, controversy, animal rights, competition, money, protection of stockholders, government regulatory power, patient rights, emotions, greed, power, personal and professional freedom, state rights, and perhaps even, ultimately, constitutional issues. As the saga of Premarin evolves, it no doubt will continue to be one of the more interesting and compelling stories of the practice of pharmacy.
The late 19th and early 20th centuries saw significant advances in our understanding of the function and structure of many endocrine hormones, including those involved with the reproductive system. Claude Bernard, a French physiologist, had discovered that glands had internal secretions which could affect other organs. In 1906, the secretion by the ovaries of a hormone that produced estrus was discovered, and the term estrogen came into use. By 1930, various placental and ovarian hormones had been identified. The Canadian Medical Associa tion Journal published an article describing an estrogen complex derived from human placental tissue.1 This natural compound was called Emmenin. The demand for contraception, as well as the need to manage menopausal and reproductive system disorders, spurred development of marketable medications from these endogenous hormones. A Montreal, Canada-based firm known as Ayerst, McKenna and Harrison (Ayerst) manufactured Emmenin. It was the first oral female sex hormone developed for clinical use.
Eight years later, in 1938, a published research report indicated that a complex of estrogens could be isolated from pregnant mare urine (PMU). Ayerst determined that this equine estrogenic complex was the same as or similar to human estrogens and could be a source for an orally active commercial medication because horses produce much more urine than humans. In 1939, PMU was first processed commercially for its estrogenic components.
Ayerst began to identify the biologic and metabolic effects of these...