Mestranol/norethynodrel was the first combined oral contraceptive pill (COCP) being mestranol and norethynodrel. It sold as Enovid in the United States and as Enavid in the United Kingdom. Developed by Gregory Pincus at G. D. Searle & Company, it was first approved on June 10, 1957, by the U.S. Food and Drug Administration for treatment of menstrual disorders. The FDA approved an additional indication for use as a contraceptive on June 23, 1960, though it only became legally prescribable nationwide and regardless of the woman's marital status after Eisenstadt v. Baird in 1972.
In 1961, it was approved as a contraceptive in the UK and in Canada.
Mestranol/noretynodrel was indicated in the treatment of gynecological and menstrual disorders. Originally it was not legal to use contraception so it was marketed for menstrual relief with the side effect of inability to conceive. It has also been used to suppress lactation and to treat endometriosis in women.
The medication contained 0.15 mg mestranol and 10 mg noretynodrel. Additional formulations containing 0.075 mg mestranol and 5 mg noretynodrel as well as 0.1 mg mestranol and 2.5 mg noretynodrel were subsequently introduced. One formulation also contained 0.075 mg mestranol and 3 mg noretynodrel.
The first published case report of a blood clot and pulmonary embolism in a woman using Enavid (Enovid 10 mg in the U.S.) at a dose of 20 mg/day did not appear until November 1961, four years after its approval, by which time it had been used by over one million women. It would take almost a decade of epidemiological studies to conclusively establish an increased risk of venous thrombosis in oral contraceptive users and an increased risk of stroke and myocardial infarction in oral contraceptive users who smoke or have high blood pressure or other cardiovascular or cerebrovascular risk factors. These risks of oral contraceptives were dramatized in the 1969 book The Doctors' Case Against the Pill by feminist journalist Barbara Seaman who helped arrange the 1970 Nelson Pill Hearings called by Senator Gaylord Nelson.
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